Skip to main content

Matthew James Hilton

Associate Professor in Orthopaedic Surgery
Orthopaedic Surgery
450 Research Drive, LSRC B321C, DUMC 91009, Durham, NC 27710
91009, Durham, NC 27710

Selected Publications


Risk factors for intracellular fatty accumulation in rotator cuff muscle: a histologic analysis.

Journal Article J Shoulder Elbow Surg · April 2024 BACKGROUND: Fatty accumulation in rotator cuff muscles has been associated with shoulder dysfunction, risk of repair failure, and poor postoperative outcomes. This study sought to assess risk factors associated with true fatty accumulation based on histolo ... Full text Link to item Cite

Radiation-induced bone loss in mice is ameliorated by inhibition of HIF-2α in skeletal progenitor cells.

Journal Article Sci Transl Med · November 29, 2023 Radiotherapy remains a common treatment modality for cancer despite skeletal complications. However, there are currently no effective treatments for radiation-induced bone loss, and the consequences of radiotherapy on skeletal progenitor cell (SPC) surviva ... Full text Link to item Cite

Association Between Supraspinatus Tendon Retraction, Histologic Myofiber Size, and Supraspinatus Muscle Atrophy on MRI.

Journal Article Am J Sports Med · July 2023 BACKGROUND: Atrophy of the rotator cuff is a negative prognostic indicator after rotator cuff repair. Although full-thickness rotator cuff tears accompanied by tendon retraction are commonly associated with decreased muscle cross-sectional area (CSA) on ma ... Full text Link to item Cite

Data from Whole-Exome Sequencing of Radiation-Induced Thymic Lymphoma in Mouse Models Identifies Notch1 Activation as a Driver of p53 Wild-Type Lymphoma

Other · March 31, 2023 <div>Abstract<p>Mouse models of radiation-induced thymic lymphoma are widely used to study the development of radiation-induced blood cancers and to gain insights into the biology of human T-cell lymphoblastic leukemia/lymphoma. Here we ... Full text Cite

Data from Whole-Exome Sequencing of Radiation-Induced Thymic Lymphoma in Mouse Models Identifies Notch1 Activation as a Driver of p53 Wild-Type Lymphoma

Other · March 31, 2023 <div>Abstract<p>Mouse models of radiation-induced thymic lymphoma are widely used to study the development of radiation-induced blood cancers and to gain insights into the biology of human T-cell lymphoblastic leukemia/lymphoma. Here we ... Full text Cite

Aged G Protein-Coupled Receptor Kinase 3 (Grk3)-Deficient Mice Exhibit Enhanced Osteoclastogenesis and Develop Bone Lesions Analogous to Human Paget's Disease of Bone.

Journal Article Cells · March 23, 2023 Paget's Disease of Bone (PDB) is a metabolic bone disease that is characterized by dysregulated osteoclast function leading to focal abnormalities of bone remodeling. It can lead to pain, fracture, and bone deformity. G protein-coupled receptor kinase 3 (G ... Full text Link to item Cite

Risk factors for intracellular fatty accumulation in rotator cuff muscle: a histologic analysis.

Journal Article J Shoulder Elbow Surg · April 2024 BACKGROUND: Fatty accumulation in rotator cuff muscles has been associated with shoulder dysfunction, risk of repair failure, and poor postoperative outcomes. This study sought to assess risk factors associated with true fatty accumulation based on histolo ... Full text Link to item Cite

Radiation-induced bone loss in mice is ameliorated by inhibition of HIF-2α in skeletal progenitor cells.

Journal Article Sci Transl Med · November 29, 2023 Radiotherapy remains a common treatment modality for cancer despite skeletal complications. However, there are currently no effective treatments for radiation-induced bone loss, and the consequences of radiotherapy on skeletal progenitor cell (SPC) surviva ... Full text Link to item Cite

Association Between Supraspinatus Tendon Retraction, Histologic Myofiber Size, and Supraspinatus Muscle Atrophy on MRI.

Journal Article Am J Sports Med · July 2023 BACKGROUND: Atrophy of the rotator cuff is a negative prognostic indicator after rotator cuff repair. Although full-thickness rotator cuff tears accompanied by tendon retraction are commonly associated with decreased muscle cross-sectional area (CSA) on ma ... Full text Link to item Cite

Data from Whole-Exome Sequencing of Radiation-Induced Thymic Lymphoma in Mouse Models Identifies Notch1 Activation as a Driver of p53 Wild-Type Lymphoma

Other · March 31, 2023 <div>Abstract<p>Mouse models of radiation-induced thymic lymphoma are widely used to study the development of radiation-induced blood cancers and to gain insights into the biology of human T-cell lymphoblastic leukemia/lymphoma. Here we ... Full text Cite

Data from Whole-Exome Sequencing of Radiation-Induced Thymic Lymphoma in Mouse Models Identifies Notch1 Activation as a Driver of p53 Wild-Type Lymphoma

Other · March 31, 2023 <div>Abstract<p>Mouse models of radiation-induced thymic lymphoma are widely used to study the development of radiation-induced blood cancers and to gain insights into the biology of human T-cell lymphoblastic leukemia/lymphoma. Here we ... Full text Cite

Aged G Protein-Coupled Receptor Kinase 3 (Grk3)-Deficient Mice Exhibit Enhanced Osteoclastogenesis and Develop Bone Lesions Analogous to Human Paget's Disease of Bone.

Journal Article Cells · March 23, 2023 Paget's Disease of Bone (PDB) is a metabolic bone disease that is characterized by dysregulated osteoclast function leading to focal abnormalities of bone remodeling. It can lead to pain, fracture, and bone deformity. G protein-coupled receptor kinase 3 (G ... Full text Link to item Cite

Magic angle effect on diffusion tensor imaging in ligament and brain.

Journal Article Magn Reson Imaging · October 2022 PURPOSE: To evaluate the magic angle effect on diffusion tensor imaging (DTI) measurements in rat ligaments and mouse brains. METHODS: Three rat knee joints and three mouse brains were scanned at 9.4 T using a modified 3D diffusion-weighted spin echo pulse ... Full text Link to item Cite

Interleukin-6 signaling mediates cartilage degradation and pain in posttraumatic osteoarthritis in a sex-specific manner.

Journal Article Sci Signal · July 26, 2022 Osteoarthritis (OA) and posttraumatic OA (PTOA) are caused by an imbalance in catabolic and anabolic processes in articular cartilage and proinflammatory changes throughout the joint, leading to joint degeneration and pain. We examined whether interleukin- ... Full text Link to item Cite

Histologic Differences in Human Rotator Cuff Muscle Based on Tear Characteristics.

Journal Article J Bone Joint Surg Am · July 6, 2022 BACKGROUND: Fatty accumulation in the rotator cuff is associated with shoulder dysfunction and a risk of failure of rotator cuff repair. The aims of this study were to (1) describe cellular findings in rotator cuff muscles in patients presenting with varyi ... Full text Link to item Cite

Identification of distinct non-myogenic skeletal-muscle-resident mesenchymal cell populations.

Journal Article Cell Rep · May 10, 2022 Mesenchymal progenitors of the lateral plate mesoderm give rise to various cell fates within limbs, including a heterogeneous group of muscle-resident mesenchymal cells. Often described as fibro-adipogenic progenitors, these cells are key players in muscle ... Full text Open Access Link to item Cite

Hypertrophic chondrocytes serve as a reservoir for marrow-associated skeletal stem and progenitor cells, osteoblasts, and adipocytes during skeletal development.

Journal Article Elife · February 18, 2022 Hypertrophic chondrocytes give rise to osteoblasts during skeletal development; however, the process by which these non-mitotic cells make this transition is not well understood. Prior studies have also suggested that skeletal stem and progenitor cells (SS ... Full text Link to item Cite

G protein-coupled receptor kinase 3 modulates mesenchymal stem cell proliferation and differentiation through sphingosine-1-phosphate receptor regulation.

Journal Article Stem Cell Res Ther · January 29, 2022 BACKGROUND: The bone marrow niche supports hematopoietic cell development through intimate contact with multipotent stromal mesenchymal stem cells; however, the intracellular signaling, function, and regulation of such supportive niche cells are still bein ... Full text Open Access Link to item Cite

HES1 is a novel downstream modifier of the SHH-GLI3 Axis in the development of preaxial polydactyly.

Journal Article PLoS Genet · December 2021 Sonic Hedgehog/GLI3 signaling is critical in regulating digit number, such that Gli3-deficiency results in polydactyly and Shh-deficiency leads to digit number reductions. SHH/GLI3 signaling regulates cell cycle factors controlling mesenchymal cell prolife ... Full text Link to item Cite

Effect of surface topography on in vitro osteoblast function and mechanical performance of 3D printed titanium.

Journal Article J Biomed Mater Res A · October 2021 Critical-sized defects remain a significant challenge in orthopaedics. 3D printed scaffolds are a promising treatment but are still limited due to inconsistent osseous integration. The goal of the study is to understand how changing the surface roughness o ... Full text Open Access Link to item Cite

Interleukin-6 Signaling Mediates Cartilage Degradation and Pain in Post-Traumatic Osteoarthritis

Journal Article · September 8, 2021 AbstractOsteoarthritis (OA) and post-traumatic OA (PTOA) are prevalent joint disorders and leading causes of chronic pain. The disease pathology of OA/PTOA is caused by imbalanced catabolic and anabolic responses and pro-in ... Full text Cite

STING suppresses bone cancer pain via immune and neuronal modulation.

Journal Article Nat Commun · July 27, 2021 Patients with advanced stage cancers frequently suffer from severe pain as a result of bone metastasis and bone destruction, for which there is no efficacious treatment. Here, using multiple mouse models of bone cancer, we report that agonists of the immun ... Full text Link to item Cite

Whole-Exome Sequencing of Radiation-Induced Thymic Lymphoma in Mouse Models Identifies Notch1 Activation as a Driver of p53 Wild-Type Lymphoma.

Journal Article Cancer Res · July 15, 2021 Mouse models of radiation-induced thymic lymphoma are widely used to study the development of radiation-induced blood cancers and to gain insights into the biology of human T-cell lymphoblastic leukemia/lymphoma. Here we aimed to identify key oncogenic dri ... Full text Link to item Cite

Hypoxia depletes contaminating CD45+ hematopoietic cells from murine bone marrow stromal cell (BMSC) cultures: Methods for BMSC culture purification.

Journal Article Stem Cell Res · May 2021 Culture expanded bone marrow stromal cells (BMSCs) are easily isolated, can be grown rapidly en masse, and contain both skeletal stem cells (SSCs) and multipotent mesenchymal progenitors (MMPs). Despite this functional heterogeneity, BMSCs continue to be u ... Full text Link to item Cite

Demineralized Murine Skeletal Histology.

Journal Article Methods Mol Biol · 2021 Cartilage and bone are specialized skeletal tissues composed of unique extracellular matrices. Bone, in particular, has a highly calcified or mineralized matrix that makes microtomy and standard histological studies very challenging. Therefore, methods to ... Full text Link to item Cite

Whole Mount In Situ Hybridization in Murine Tissues.

Journal Article Methods Mol Biol · 2021 Whole mount in situ hybridization is a sensitive method used to characterize the spatial and temporal expression of RNA transcripts throughout an entire tissue. This method is an excellent tool for studying gene expression during embryonic development. Her ... Full text Link to item Cite

Isolation and Culture of Murine Primary Chondrocytes: Costal and Growth Plate Cartilage.

Journal Article Methods Mol Biol · 2021 Primary chondrocyte isolation and culture is a useful tool to characterize how cellular perturbations impact chondrocyte behavior and mineralization in vitro. This protocol conveys methods for isolating and culturing primary chondrocytes from costal and gr ... Full text Link to item Cite

Preface

Book · January 1, 2021 Cite

STING suppresses cancer pain via immune and neuronal modulation

Journal Article · 2021 Agonists of the innate immune regulator stimulator of interferon genes (STING) have shown great efficacy in promoting antitumor immunity in preclinical models, leading to their exploration in cancer immunotherapy trials. Patients with advanced stage cancer ... Full text Cite

Characterization complex collagen fiber architecture in knee joint using high-resolution diffusion imaging.

Journal Article Magn Reson Med · August 2020 PURPOSE: To evaluate the complex fiber orientations and 3D collagen fiber network of knee joint connective tissues, including ligaments, muscle, articular cartilage, and meniscus using high spatial and angular resolution diffusion imaging. METHODS: Two rat ... Full text Open Access Link to item Cite

PD-1 blockade inhibits osteoclast formation and murine bone cancer pain.

Journal Article J Clin Invest · July 1, 2020 Emerging immune therapy, such as with the anti-programmed cell death-1 (anti-PD-1) monoclonal antibody nivolumab, has shown efficacy in tumor suppression. Patients with terminal cancer suffer from cancer pain as a result of bone metastasis and bone destruc ... Full text Link to item Cite

HES1 is a Critical Mediator of the SHH-GLI3 Axis in Regulating Digit Number

Journal Article · 2020 ABSTRACT Sonic Hedgehog/GLI3 signaling is critical in regulating digit number, such that Gli3-deficiency results in polydactyly and Shh-deficiency leads to digit number reductions. Anterior-posterior SHH/GLI3 signaling gradients regulate cell cycl ... Full text Cite

Dysregulation of STAT3 signaling is associated with endplate-oriented herniations of the intervertebral disc in Adgrg6 mutant mice.

Journal Article PLoS Genet · October 2019 Degenerative changes of the intervertebral disc (IVD) are a leading cause of disability affecting humans worldwide and has been attributed primarily to trauma and the accumulation of pathology during aging. While genetic defects have also been associated w ... Full text Link to item Cite

Chondrocyte-Specific RUNX2 Overexpression Accelerates Post-traumatic Osteoarthritis Progression in Adult Mice.

Journal Article J Bone Miner Res · September 2019 RUNX2 is a transcription factor critical for chondrocyte maturation and normal endochondral bone formation. It promotes the expression of factors catabolic to the cartilage extracellular matrix and is upregulated in human osteoarthritic cartilage and in mu ... Full text Link to item Cite

The CaV1.2 L-type calcium channel regulates bone homeostasis in the middle and inner ear.

Journal Article Bone · August 2019 Bone remodeling of the auditory ossicles and the otic capsule is highly restricted and tightly controlled by the osteoprotegerin (OPG)/receptor activator of nuclear factor kappa-Β ligand (RANKL)/receptor activator of nuclear factor kappa-Β (RANK) system. I ... Full text Link to item Cite

Diffusion tractography of the rat knee at microscopic resolution.

Journal Article Magn Reson Med · June 2019 PURPOSE: To evaluate whole knee joint tractography, including articular cartilage, ligaments, meniscus, and growth plate using diffusion tensor imaging (DTI) at microscopic resolution. METHODS: Three rat knee joints were scanned using a modified 3D diffusi ... Full text Link to item Cite

Glutamine Metabolism Regulates Proliferation and Lineage Allocation in Skeletal Stem Cells.

Journal Article Cell Metab · April 2, 2019 Skeletal stem cells (SSCs) are postulated to provide a continuous supply of osteoblasts throughout life. However, under certain conditions, the SSC population can become incorrectly specified or is not maintained, resulting in reduced osteoblast formation, ... Full text Link to item Cite

Application of genetically modified animals in bone research

Chapter · January 1, 2019 Genetically modified mice have had an enormous impact on our understanding of skeletal development, maintenance, and disease. Publicly supported efforts to generate and phenotype genes in the mouse have greatly expanded the ease of identifying and characte ... Full text Cite

Intracellular biosynthesis of lipids and cholesterol by Scap and Insig in mesenchymal cells regulates long bone growth and chondrocyte homeostasis.

Journal Article Development · July 9, 2018 During enchondral ossification, mesenchymal cells express genes regulating the intracellular biosynthesis of cholesterol and lipids. Here, we have investigated conditional deletion of Scap or of Insig1 and Insig2 (Scap inhibits intracellular biosynthesis a ... Full text Link to item Cite

Cell type-specific effects of Notch signaling activation on intervertebral discs: Implications for intervertebral disc degeneration.

Journal Article J Cell Physiol · July 2018 Intervertebral disc (IVD) degeneration is the major cause of back pain. Notch signaling is activated in annulus fibrosus (AF) and nucleus pulposus (NP) tissues of degenerated IVDs, and induced by IL1-β and TNF-α in NP cells. However, the role of Notch acti ... Full text Link to item Cite

Endochondral ossification

Chapter · January 1, 2018 The endochondral ossification, the process responsible for generating most of the skeleton, requires a cartilage intermediate before forming bone. This chapter discusses the major cellular events of endochondral ossification: chondrogenesis, chondrocyte hy ... Full text Cite

Increased Ca2+ signaling through CaV1.2 promotes bone formation and prevents estrogen deficiency-induced bone loss.

Journal Article JCI Insight · November 16, 2017 While the prevalence of osteoporosis is growing rapidly with population aging, therapeutic options remain limited. Here, we identify potentially novel roles for CaV1.2 L-type voltage-gated Ca2+ channels in osteogenesis and exploit a transgenic gain-of-func ... Full text Link to item Cite

The Notch Ligand Jagged1 Regulates the Osteoblastic Lineage by Maintaining the Osteoprogenitor Pool.

Journal Article J Bone Miner Res · June 2017 Notch signaling is critical for osteoblastic differentiation; however, the specific contribution of individual Notch ligands is unknown. Parathyroid hormone (PTH) regulates the Notch ligand Jagged1 in osteoblastic cells. To determine if osteolineage Jagged ... Full text Link to item Cite

Daily oral consumption of hydrolyzed type 1 collagen is chondroprotective and anti-inflammatory in murine posttraumatic osteoarthritis.

Journal Article PLoS One · 2017 Osteoarthritis (OA) is a degenerative joint disease for which there are no disease modifying therapies. Thus, strategies that offer chondroprotective or regenerative capability represent a critical unmet need. Recently, oral consumption of a hydrolyzed typ ... Full text Link to item Cite

Use of Hes1-GFP reporter mice to assess activity of the Hes1 promoter in bone cells under chronic inflammation.

Journal Article Bone · September 2016 Notch signaling plays a critical role in maintaining bone homeostasis partially by controlling the formation of osteoblasts from mesenchymal stem cells (MSCs). We reported that TNF activates Notch signaling in MSCs which inhibits osteoblast differentiation ... Full text Link to item Cite

Suppressive Effects of Insulin on Tumor Necrosis Factor-Dependent Early Osteoarthritic Changes Associated With Obesity and Type 2 Diabetes Mellitus.

Journal Article Arthritis Rheumatol · June 2016 OBJECTIVE: Obesity is a state of chronic inflammation that is associated with insulin resistance and type 2 diabetes mellitus (DM), as well as an increased risk of osteoarthritis (OA). This study was undertaken to define the links between obesity-associate ... Full text Link to item Cite

HES factors regulate specific aspects of chondrogenesis and chondrocyte hypertrophy during cartilage development.

Journal Article J Cell Sci · June 1, 2016 RBPjκ-dependent Notch signaling regulates multiple processes during cartilage development, including chondrogenesis, chondrocyte hypertrophy and cartilage matrix catabolism. Select members of the HES- and HEY-families of transcription factors are recognize ... Full text Link to item Cite

Notch signaling indirectly promotes chondrocyte hypertrophy via regulation of BMP signaling and cell cycle arrest.

Journal Article Sci Rep · May 5, 2016 Cell cycle regulation is critical for chondrocyte differentiation and hypertrophy. Recently we identified the Notch signaling pathway as an important regulator of chondrocyte proliferation and differentiation during mouse cartilage development. To investig ... Full text Link to item Cite

Notch signaling in postnatal joint chondrocytes, but not subchondral osteoblasts, is required for articular cartilage and joint maintenance.

Journal Article Osteoarthritis Cartilage · April 2016 OBJECTIVE: Notch signaling has been identified as a critical regulator in cartilage development and joint maintenance, and loss of Notch signaling in all joint tissues results in an early and progressive osteoarthritis (OA)-like pathology. This study inves ... Full text Link to item Cite

NOTCH signaling in skeletal progenitors is critical for fracture repair.

Journal Article J Clin Invest · April 1, 2016 Fracture nonunions develop in 10%-20% of patients with fractures, resulting in prolonged disability. Current data suggest that bone union during fracture repair is achieved via proliferation and differentiation of skeletal progenitors within periosteal and ... Full text Link to item Cite

CCN1 Regulates Chondrocyte Maturation and Cartilage Development.

Journal Article J Bone Miner Res · March 2016 WNT/β-CATENIN signaling is involved in multiple aspects of skeletal development, including chondrocyte differentiation and maturation. Although the functions of β-CATENIN in chondrocytes have been extensively investigated through gain-of-function and loss- ... Full text Link to item Cite

Transient gamma-secretase inhibition accelerates and enhances fracture repair likely via Notch signaling modulation.

Journal Article Bone · April 2015 Approximately 10% of skeletal fractures result in healing complications and non-union, while most fractures repair with appropriate stabilization and without pharmacologic intervention. It is the latter injuries that cannot be underestimated as the expense ... Full text Link to item Cite

PTH receptor signaling in osteoblasts regulates endochondral vascularization in maintenance of postnatal growth plate.

Journal Article J Bone Miner Res · February 2015 Longitudinal growth of postnatal bone requires precise control of growth plate cartilage chondrocytes and subsequent osteogenesis and bone formation. Little is known about the role of angiogenesis and bone remodeling in maintenance of cartilaginous growth ... Full text Link to item Cite

Notch signaling controls chondrocyte hypertrophy via indirect regulation of Sox9.

Journal Article Bone Res · 2015 RBPjk-dependent Notch signaling regulates both the onset of chondrocyte hypertrophy and the progression to terminal chondrocyte maturation during endochondral ossification. It has been suggested that Notch signaling can regulate Sox9 transcription, althoug ... Full text Link to item Cite

NOTCH-Mediated Maintenance and Expansion of Human Bone Marrow Stromal/Stem Cells: A Technology Designed for Orthopedic Regenerative Medicine.

Journal Article Stem Cells Transl Med · December 2014 Featured Publication Human bone marrow-derived stromal/stem cells (BMSCs) have great therapeutic potential for treating skeletal disease and facilitating skeletal repair, although maintaining their multipotency and expanding these cells ex vivo have proven difficult. Because m ... Full text Link to item Cite

Multiple hereditary exostoses (MHE): elucidating the pathogenesis of a rare skeletal disorder through interdisciplinary research.

Journal Article Connect Tissue Res · April 2014 Abstract An interdisciplinary and international group of clinicians and scientists gathered in Philadelphia, PA, to attend the fourth International Research Conference on Multiple Hereditary Exostoses (MHE), a rare and severe skeletal disorder. MHE is larg ... Full text Link to item Cite

The effect of mesenchymal stem cell sheets on structural allograft healing of critical sized femoral defects in mice.

Journal Article Biomaterials · March 2014 Structural bone allografts are widely used in the clinic to treat critical sized bone defects, despite lacking the osteoinductive characteristics of live autografts. To address this, we generated revitalized structural allografts wrapped with mesenchymal s ... Full text Link to item Cite

Isolation and culture of murine primary chondrocytes.

Journal Article Methods Mol Biol · 2014 To identify factors that are necessary and sufficient for chondrocyte hypertrophic differentiation and cartilage matrix mineralization, primary chondrocyte culture models have been developed. Here we describe the isolation, short-term and long-term culture ... Full text Link to item Cite

Demineralized murine skeletal histology.

Journal Article Methods Mol Biol · 2014 Cartilage and bone are specialized skeletal tissues composed of unique extracellular matrices. Bone, in particular, has a highly calcified or mineralized matrix that makes microtomy and standard histological studies very challenging. Therefore, methods to ... Full text Link to item Cite

Whole-mount in situ hybridization on murine skeletogenic tissues.

Journal Article Methods Mol Biol · 2014 Whole-mount in situ hybridization (WISH) is a highly sensitive method for spatial and temporal visualization of RNA transcripts throughout an entire tissue. This method is an excellent tool for studying both embryonic development and disease. It is based o ... Full text Link to item Cite

Delayed fracture healing and increased callus adiposity in a C57BL/6J murine model of obesity-associated type 2 diabetes mellitus.

Journal Article PLoS One · 2014 INTRODUCTION: Impaired healing and non-union of skeletal fractures is a major public health problem, with morbidity exacerbated in patients with diabetes mellitus (DM). DM is prevalent worldwide and affects approximately 25.8 million US adults, with >90% h ... Full text Link to item Cite

Demineralized murine skeletal histology

Journal Article Methods in Molecular Biology · January 1, 2014 Cartilage and bone are specialized skeletal tissues composed of unique extracellular matrices. Bone, in particular, has a highly calcified or mineralized matrix that makes microtomy and standard histological studies very challenging. Therefore, methods to ... Full text Cite

Isolation and culture of murine primary chondrocytes

Journal Article Methods in Molecular Biology · January 1, 2014 To identify factors that are necessary and sufficient for chondrocyte hypertrophic differentiation and cartilage matrix mineralization, primary chondrocyte culture models have been developed. Here we describe the isolation, short-term and long-term culture ... Full text Cite

Preface

Journal Article Methods in Molecular Biology · January 1, 2014 Full text Cite

Whole-mount in situ hybridization on murine skeletogenic tissues

Journal Article Methods in Molecular Biology · January 1, 2014 Whole-mount in situ hybridization (WISH) is a highly sensitive method for spatial and temporal visualization of RNA transcripts throughout an entire tissue. This method is an excellent tool for studying both embryonic development and disease. It is based o ... Full text Cite

TAK1 regulates SOX9 expression in chondrocytes and is essential for postnatal development of the growth plate and articular cartilages.

Journal Article J Cell Sci · December 15, 2013 TAK1 is a MAP3K that mediates non-canonical TGF-β and BMP signaling. During the embryonic period, TAK1 is essential for cartilage and joint development as deletion of Tak1 in chondro-osteo progenitor cells leads to severe chondrodysplasia with defects in b ... Full text Link to item Cite

RBP-Jκ-dependent Notch signaling is required for murine articular cartilage and joint maintenance.

Journal Article Arthritis Rheum · October 2013 OBJECTIVE: Osteoarthritis (OA) is a degenerative disease resulting in severe joint cartilage destruction and disability. While the mechanisms underlying the development and progression of OA are poorly understood, gene mutations have been identified within ... Full text Link to item Cite

Troponin T3 expression in skeletal and smooth muscle is required for growth and postnatal survival: characterization of Tnnt3(tm2a(KOMP)Wtsi) mice.

Journal Article Genesis · September 2013 The troponin complex, which consists of three regulatory proteins (troponin C, troponin I, and troponin T), is known to regulate muscle contraction in skeletal and cardiac muscle, but its role in smooth muscle remains controversial. Troponin T3 (TnnT3) is ... Full text Link to item Cite

Engineering superficial zone features in tissue engineered cartilage.

Journal Article Biotechnol Bioeng · May 2013 A major challenge in cartilage tissue engineering is the need to recreate the native tissue's anisotropic extracellular matrix structure. This anisotropy has important mechanical and biological consequences and could be crucial for integrative repair. Here ... Full text Link to item Cite

Mouse models of joint disorders

Conference Osteoarthritis and Cartilage · April 2013 Full text Cite

Cartilage-specific β-catenin signaling regulates chondrocyte maturation, generation of ossification centers, and perichondrial bone formation during skeletal development.

Journal Article J Bone Miner Res · August 2012 The WNT/β-catenin signaling pathway is a critical regulator of chondrocyte and osteoblast differentiation during multiple phases of cartilage and bone development. Although the importance of β-catenin signaling during the process of endochondral bone devel ... Full text Link to item Cite

Ski inhibits TGF-β/phospho-Smad3 signaling and accelerates hypertrophic differentiation in chondrocytes.

Journal Article J Cell Biochem · June 2012 Since transforming growing factor-β (TGF-β)/Smad signaling inhibits chondrocyte maturation, endogenous negative regulators of TGF-β signaling are likely also important regulators of the chondrocyte differentiation process. One such negative regulator, Ski, ... Full text Link to item Cite

Cartilage-specific RBPjκ-dependent and -independent Notch signals regulate cartilage and bone development.

Journal Article Development · March 2012 Featured Publication The Notch signaling pathway has emerged as an important regulator of endochondral bone formation. Although recent studies have examined the role of Notch in mesenchymal and chondro-osteo progenitor cell populations, there has yet to be a true examination o ... Full text Link to item Cite

BMP2, but not BMP4, is crucial for chondrocyte proliferation and maturation during endochondral bone development.

Journal Article J Cell Sci · October 15, 2011 The BMP signaling pathway has a crucial role in chondrocyte proliferation and maturation during endochondral bone development. To investigate the specific function of the Bmp2 and Bmp4 genes in growth plate chondrocytes during cartilage development, we gen ... Full text Link to item Cite

Teriparatide as a chondroregenerative therapy for injury-induced osteoarthritis.

Journal Article Sci Transl Med · September 21, 2011 There is no disease-modifying therapy for osteoarthritis, a degenerative joint disease that is projected to afflict more than 67 million individuals in the United States alone by 2030. Because disease pathogenesis is associated with inappropriate articular ... Full text Link to item Cite

TNF is required for the induction but not the maintenance of compression-induced BME signals in murine tail vertebrae: limitations of anti-TNF therapy for degenerative disc disease.

Journal Article J Orthop Res · September 2011 While bone marrow edema (BME) is diagnostic of spondyloarthropathy, its nature remains poorly understood. In contrast, BME in ankylosing spondylitis is caused by tumor necrosis factor (TNF)-induced vascular and cellular changes. To investigate the relation ... Full text Link to item Cite

Establishment of an index with increased sensitivity for assessing murine arthritis.

Journal Article J Orthop Res · August 2011 The goals of our study were to establish quantitative outcomes for assessing murine knee arthritis and develop an Arthritis Index that incorporates multiple outcomes into a single calculation that provides enhanced sensitivity. Using an accepted model of m ... Full text Link to item Cite

Impact of Smad3 loss of function on scarring and adhesion formation during tendon healing.

Journal Article J Orthop Res · May 2011 Studies were performed evaluating the role of Smad3, a transcription factor mediating canonical TGF-β signaling, on scarring and adhesion formation using an established flexor digitorum longus (FDL) tendon repair model. In unoperated animals the metatarsop ... Full text Link to item Cite

Chronic axial compression of the mouse tail segment induces MRI bone marrow edema changes that correlate with increased marrow vasculature and cellularity.

Journal Article J Orthop Res · September 2010 Magnetic resonance imaging (MRI) of bone marrow edema (BME) has been found to be helpful in the diagnosis of back pain attributed to degenerative disk disease (DDD) and spondyloarthropathy (SA), but its interpretation is limited by a lack of knowledge of i ... Full text Link to item Cite

TAK1 regulates cartilage and joint development via the MAPK and BMP signaling pathways.

Journal Article J Bone Miner Res · August 2010 The importance of canonical transforming growth factor beta (TGF-beta) and bone morphogenetic protein (BMP) signaling during cartilage and joint development is well established, but the necessity for noncanonical (SMAD-independent) signaling during these p ... Full text Link to item Cite

RBPjkappa-dependent Notch signaling regulates mesenchymal progenitor cell proliferation and differentiation during skeletal development.

Journal Article Development · May 2010 Featured Publication The Notch pathway has recently been implicated in mesenchymal progenitor cell (MPC) differentiation from bone marrow-derived progenitors. However, whether Notch regulates MPC differentiation in an RBPjkappa-dependent manner, specifies a particular MPC cell ... Full text Link to item Cite

Axin2 regulates chondrocyte maturation and axial skeletal development.

Journal Article J Orthop Res · January 2010 Axis inhibition proteins 1 and 2 (Axin1 and Axin2) are scaffolding proteins that modulate at least two signaling pathways that are crucial in skeletogenesis: the Wnt/beta-catenin and TGF-beta signaling pathways. To determine whether Axin2 is important in s ... Full text Link to item Cite

Suppression of CXCL12 production by bone marrow osteoblasts is a common and critical pathway for cytokine-induced mobilization.

Journal Article Blood · August 13, 2009 Current evidence suggests that hematopoietic stem/progenitor cell (HSPC) mobilization by granulocyte colony-stimulating factor (G-CSF) is mediated by induction of bone marrow proteases, attenuation of adhesion molecule function, and disruption of CXCL12/CX ... Full text Link to item Cite

Efficacy of colistin-impregnated beads to prevent multidrug-resistant A. baumannii implant-associated osteomyelitis.

Journal Article J Orthop Res · August 2009 Osteomyelitis (OM) from multidrug-resistant (MDR) Acinetobacter has emerged in >30% of combat-related injuries in Iraq and Afghanistan. While most of these strains are sensitive to colistin, the drug is not available in bone void fillers for local high-dos ... Full text Link to item Cite

Mechanism of shortened bones in mucopolysaccharidosis VII.

Journal Article Mol Genet Metab · July 2009 Mucopolysaccharidosis VII (MPS VII) is a lysosomal storage disease in which deficiency in beta-glucuronidase results in glycosaminoglycan (GAG) accumulation in and around cells, causing shortened long bones through mechanisms that remain largely unclear. W ... Full text Link to item Cite

An FGF-WNT gene regulatory network controls lung mesenchyme development.

Journal Article Dev Biol · July 15, 2008 Lung mesenchyme is a critical determinant of the shape and size of the lung, the extent and patterning of epithelial branching, and the formation of the pulmonary vasculature and interstitial mesenchymal components of the adult lung. Fibroblast growth fact ... Full text Link to item Cite

Rac1 activation controls nuclear localization of beta-catenin during canonical Wnt signaling.

Journal Article Cell · April 18, 2008 Canonical Wnt signaling critically regulates cell fate and proliferation in development and disease. Nuclear localization of beta-catenin is indispensable for canonical Wnt signaling; however, the mechanisms governing beta-catenin nuclear localization are ... Full text Link to item Cite

NOTCH1 regulates osteoclastogenesis directly in osteoclast precursors and indirectly via osteoblast lineage cells.

Journal Article J Biol Chem · March 7, 2008 NOTCH signaling is a key regulator of cell fate decisions in prenatal skeletal development and is active during adult tissue renewal. In addition, its association with neoplasia suggests that it is a candidate therapeutic target. We find that attenuated NO ... Full text Link to item Cite

Notch signaling maintains bone marrow mesenchymal progenitors by suppressing osteoblast differentiation.

Journal Article Nat Med · March 2008 Featured Publication Postnatal bone marrow houses mesenchymal progenitor cells that are osteoblast precursors. These cells have established therapeutic potential, but they are difficult to maintain and expand in vitro, presumably because little is known about the mechanisms co ... Full text Link to item Cite

Tamoxifen-inducible gene deletion reveals a distinct cell type associated with trabecular bone, and direct regulation of PTHrP expression and chondrocyte morphology by Ihh in growth region cartilage.

Journal Article Dev Biol · August 1, 2007 Indian hedgehog (Ihh) controls multiple aspects of endochondral skeletal development by signaling to both chondrocytes and perichondrial cells. Previous efforts to delineate direct effects of Ihh on chondrocytes by Col2-Cre-mediated ablation of Smoothened ... Full text Link to item Cite

Chromosome 8

Journal Article · April 16, 2007 AbstractChromosome 8 is a submetacentric chromosome containing about 5% of the euchromatic human genome that is associated with approximately 96 diseases or syndromes. Notably, it contains a region of strikingly high mutati ... Full text Cite

Notch signaling represses osteoblast activity but promotes osteoclast function in vivo.

Conference JOURNAL OF BONE AND MINERAL RESEARCH · September 1, 2006 Link to item Cite

Ihh controls cartilage development by antagonizing Gli3, but requires additional effectors to regulate osteoblast and vascular development.

Journal Article Development · October 2005 Indian hedgehog (Ihh) controls multiple aspects of endochondral skeletal development, including proliferation and maturation of chondrocytes, osteoblast development and cartilage vascularization. Although it is known that Gli transcription factors are key ... Full text Link to item Cite

EXT1 regulates chondrocyte proliferation and differentiation during endochondral bone development.

Journal Article Bone · March 2005 Multiple Hereditary Exostoses (MHE) is an autosomal dominant skeletal disorder most frequently caused by mutations in the EXT1 gene. MHE affects proper development of endochondral bones, such that all affected individuals present with exostoses adjacent to ... Full text Link to item Cite

Sequential roles of Hedgehog and Wnt signaling in osteoblast development.

Journal Article Development · January 2005 Signals that govern development of the osteoblast lineage are not well understood. Indian hedgehog (Ihh), a member of the hedgehog (Hh) family of proteins, is essential for osteogenesis in the endochondral skeleton during embryogenesis. The canonical pathw ... Full text Link to item Cite

Analysis of novel and recurrent mutations responsible for the tricho-rhino-phalangeal syndromes.

Journal Article J Hum Genet · 2002 The tricho-rhino-phalangeal syndromes (TRPS type I, II, and III) are autosomal dominant disorders sharing the following characteristics: slowly growing and sparse scalp hair, medially thick and laterally thin eyebrows, bulbous tip of the nose, long flat ph ... Full text Link to item Cite

An integrated physical map of 8q22-q24: use in positional cloning and deletion analysis of Langer-Giedion syndrome.

Journal Article Genomics · January 15, 2001 We have developed an integrated map for a 35-cM area of human chromosome 8 surrounding the Langer-Giedion syndrome deletion region. This map spans from approximately 8q22 to 8q24 and includes 10 hybrid cell intervals, 89 polymorphic STSs, 118 ESTs, and 37 ... Full text Link to item Cite