Scholars@Duke
Amy Lynn McNulty

Amy Lynn McNulty

Associate Professor in Orthopaedic Surgery
Orthopaedic Surgery
alr@duke.edu
DUMC Box 3093, Durham, NC 27710
355A MSRB1, Durham, NC 27710

Selected Publications

Mode of injury and level of synovitis alter inflammatory chondrocyte gene expression and associated pathways.

Journal Article Sci Rep · November 21, 2024 Although various joint injuries result in post-traumatic osteoarthritis (PTOA), differences in chondrocyte response to specific injuries, such as blunt compression or fracture, are unclear. Furthermore, the role of underlying joint inflammation, or synovit ... Full text Link to item Cite

Meniscus gene expression profiling of inner and outer zone meniscus tissue compared to cartilage and passaged monolayer meniscus cells.

Journal Article Sci Rep · November 9, 2024 Meniscus injuries are common and while surgical strategies have improved, there is a need for alternative therapeutics to improve long-term outcomes and prevent post-traumatic osteoarthritis. Current research efforts in regenerative therapies and tissue en ... Full text Link to item Cite

3D melt blowing of Elastollan thermoplastic polyurethane for tissue engineering applications: A pilot study

Journal Article Manufacturing Letters · October 1, 2024 Scaffolds, in addition to being biocompatible, should possess structural and mechanical properties similar to the natural tissues they intend to replace. Many tissue engineering applications require porous 3D scaffolds characterized by unique microfibrous ... Full text Cite

Shedding light on the effects of blood on meniscus tissue: the role of mononuclear leukocytes in mediating meniscus catabolism.

Journal Article Osteoarthritis Cartilage · August 2024 OBJECTIVE: Traumatic meniscal injuries can cause acute pain, hemarthrosis (bleeding into the joint), joint immobility, and post-traumatic osteoarthritis (PTOA). However, the exact mechanism(s) by which PTOA develops following meniscal injuries is unknown. ... Full text Link to item Cite

High angular resolution diffusion imaging (HARDI) of porcine menisci: a comparison of diffusion tensor imaging and generalized q-sampling imaging.

Journal Article Quant Imaging Med Surg · April 3, 2024 BACKGROUND: Diffusion magnetic resonance imaging (MRI) allows for the quantification of water diffusion properties in soft tissues. The goal of this study was to characterize the 3D collagen fiber network in the porcine meniscus using high angular resoluti ... Full text Link to item Cite

Healthy but not osteoarthritic human meniscus-derived matrix scaffolds promote meniscus repair.

Journal Article Front Bioeng Biotechnol · 2024 Meniscus tissue is commonly injured due to sports-related injuries and age-related degeneration and approximately 50% of individuals with a meniscus tear will develop post-traumatic osteoarthritis (PTOA). Given that the meniscus has limited healing potenti ... Full text Link to item Cite

The effects of a 6-month weight loss intervention on physical function and serum biomarkers in older adults with and without osteoarthritis.

Journal Article Osteoarthr Cartil Open · September 2023 OBJECTIVE: To examine the effects of a 6-month weight loss intervention on physical function, inflammatory biomarkers, and metabolic biomarkers in both those with and without osteoarthritis (OA). DESIGN: 59 individuals ≥60 years old with obesity and a func ... Full text Link to item Cite

Analytical validation and quality control/quality assurance practices for improved rigor and reproducibility of biochemical assays in orthopaedic research.

Journal Article J Orthop Res · July 2023 Orthopaedic research, and biomedical research in general, has made enormous strides to develop treatments for conditions long thought to be inevitable or untreatable; however, there is growing concern about the quality of published research. Considerable e ... Full text Link to item Cite

The Interplay of Biomechanical and Biological Changes Following Meniscus Injury.

Journal Article Curr Rheumatol Rep · February 2023 PURPOSE OF REVIEW: Meniscus injury often leads to joint degeneration and post-traumatic osteoarthritis (PTOA) development. Therefore, the purpose of this review is to outline the current understanding of biomechanical and biological repercussions following ... Full text Link to item Cite

Combination of Lidocaine and IL-1Ra Is Effective at Reducing Degradation of Porcine Cartilage Explants.

Journal Article Am J Sports Med · June 2022 BACKGROUND: Posttraumatic inflammation after joint injury, ranging from sprains to articular fracture, contributes to the development of arthritis, and the administration of interleukin 1 (IL-1) receptor antagonist (IL-1Ra) is a potential intervention to m ... Full text Link to item Cite

A Tale of Two Loads: Modulation of IL-1 Induced Inflammatory Responses of Meniscal Cells in Two Models of Dynamic Physiologic Loading.

Journal Article Front Bioeng Biotechnol · 2022 Meniscus injuries are highly prevalent, and both meniscus injury and subsequent surgery are linked to the development of post-traumatic osteoarthritis (PTOA). Although the pathogenesis of PTOA remains poorly understood, the inflammatory cytokine IL-1 is el ... Full text Link to item Cite

Mechanical metrics may show improved ability to predict osteoarthritis compared to T1rho mapping.

Journal Article J Biomech · December 2, 2021 Changes in cartilage structure and composition are commonly observed during the progression of osteoarthritis (OA). Importantly, quantitative magnetic resonance imaging (MRI) methods, such as T1rho relaxation imaging, can noninvasively provide in vivo metr ... Full text Link to item Cite

Optimization of Meniscus Cell Transduction Using Lentivirus and Adeno-Associated Virus for Gene Editing and Tissue Engineering Applications.

Journal Article Cartilage · December 2021 OBJECTIVES: The utilization of viral vectors to deliver genes of interest directly to meniscus cells and promote long-term modulation of gene expression may prove useful to enhance meniscus repair and regeneration. The objective of this study was to optimi ... Full text Link to item Cite

Immune cell profiles in synovial fluid after anterior cruciate ligament and meniscus injuries.

Journal Article Arthritis Res Ther · November 4, 2021 BACKGROUND: Anterior cruciate ligament (ACL) and meniscus tears are common knee injuries. Despite the high rate of post-traumatic osteoarthritis (PTOA) following these injuries, the contributing factors remain unclear. In this study, we characterized the i ... Full text Open Access Link to item Cite

Meniscus cell regional phenotypes: Dedifferentiation and reversal by biomaterial embedding.

Journal Article J Orthop Res · October 2021 Meniscus injuries are common and a major cause of long-term joint degeneration and disability. Current treatment options are limited, so novel regenerative therapies or tissue engineering strategies are urgently needed. The development of new therapies is ... Full text Link to item Cite

Blood in the joint: effects of hemarthrosis on meniscus health and repair techniques.

Journal Article Osteoarthritis Cartilage · April 2021 Injury to the meniscus is common and frequently leads to the development of post-traumatic osteoarthritis (PTOA). Many times meniscus injuries occur coincident with anterior cruciate ligament (ACL) injuries and lead to a bloody joint effusion. Hemarthrosis ... Full text Link to item Cite

Inflammatory signaling sensitizes Piezo1 mechanotransduction in articular chondrocytes as a pathogenic feed-forward mechanism in osteoarthritis.

Journal Article Proc Natl Acad Sci U S A · March 30, 2021 Osteoarthritis (OA) is a painful and debilitating condition of synovial joints without any disease-modifying therapies [A. M. Valdes, T. D. Spector, Nat. Rev. Rheumatol. 7, 23-32 (2011)]. We previously identified mechanosensitive PIEZO channels, PIEZO1 and ... Full text Open Access Link to item Cite

A synthetic mechanogenetic gene circuit for autonomous drug delivery in engineered tissues.

Journal Article Sci Adv · January 2021 Mechanobiologic signals regulate cellular responses under physiologic and pathologic conditions. Using synthetic biology and tissue engineering, we developed a mechanically responsive bioartificial tissue that responds to mechanical loading to produce a pr ... Full text Link to item Cite

The Influence of Obesity and Meniscal Coverage on In Vivo Tibial Cartilage Thickness and Strain.

Journal Article Orthop J Sports Med · December 2020 BACKGROUND: Obesity, which potentially increases loading at the knee, is a common and modifiable risk factor for the development of knee osteoarthritis. The menisci play an important role in distributing joint loads to the underlying cartilage. However, th ... Full text Link to item Cite

Evaluation of culture conditions for in vitro meniscus repair model systems using bone marrow-derived mesenchymal stem cells.

Journal Article Connect Tissue Res · 2020 Purpose: Meniscal injury and loss of meniscus tissue lead to osteoarthritis development. Therefore, novel biologic strategies are needed to enhance meniscus tissue repair. The purpose of this study was to identify a favorable culture medium for both bone m ... Full text Link to item Cite

Meniscus-Derived Matrix Bioscaffolds: Effects of Concentration and Cross-Linking on Meniscus Cellular Responses and Tissue Repair.

Journal Article Int J Mol Sci · December 19, 2019 Meniscal injuries, particularly in the avascular zone, have a low propensity for healing and are associated with the development of osteoarthritis. Current meniscal repair techniques are limited to specific tear types and have significant risk for failure. ... Full text Open Access Link to item Cite

Meniscus-Derived Matrix Scaffolds Promote the Integrative Repair of Meniscal Defects.

Journal Article Sci Rep · June 18, 2019 Meniscal tears have a poor healing capacity, and damage to the meniscus is associated with significant pain, disability, and progressive degenerative changes in the knee joint that lead to osteoarthritis. Therefore, strategies to promote meniscus repair an ... Full text Open Access Link to item Cite

Osteoarthritis year in review 2018: mechanics.

Journal Article Osteoarthritis Cartilage · March 2019 OBJECTIVE: To review recent biomechanics literature focused on the interactions between biomechanics and articular cartilage health, particularly focused on macro-scale and human studies. DESIGN: A literature search was conducted in PubMed using the search ... Full text Link to item Cite

Selective Enzymatic Digestion of Proteoglycans and Collagens Alters Cartilage T1rho and T2 Relaxation Times.

Journal Article Ann Biomed Eng · January 2019 Our objective was to determine the relationship of T1rho and T2 relaxation mapping to the biochemical and biomechanical properties of articular cartilage through selective digestion of proteoglycans and collagens. Femoral condyles were harvested from porci ... Full text Link to item Cite

CXCL10 is upregulated in synovium and cartilage following articular fracture.

Journal Article J Orthop Res · April 2018 The objective of this study was to investigate the expression of the chemokine CXCL10 and its role in joint tissues following articular fracture. We hypothesized that CXCL10 is upregulated following articular fracture and contributes to cartilage degradati ... Full text Open Access Link to item 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

In Vivo Tibial Cartilage Strains in Regions of Cartilage-to-Cartilage Contact and Cartilage-to-Meniscus Contact in Response to Walking.

Journal Article Am J Sports Med · October 2017 BACKGROUND: There are currently limited human in vivo data characterizing the role of the meniscus in load distribution within the tibiofemoral joint. Purpose/Hypothesis: The purpose was to compare the strains experienced in regions of articular cartilage ... Full text Link to item Cite

Relationship between T1rho magnetic resonance imaging, synovial fluid biomarkers, and the biochemical and biomechanical properties of cartilage.

Journal Article J Biomech · April 11, 2017 Non-invasive techniques for quantifying early biochemical and biomechanical changes in articular cartilage may provide a means of more precisely assessing osteoarthritis (OA) progression. The goals of this study were to determine the relationship between T ... Full text Link to item Cite

Matrix metalloproteinase activity and prostaglandin E2 are elevated in the synovial fluid of meniscus tear patients.

Journal Article Connect Tissue Res · 2017 PURPOSE: Meniscus tears are a common knee injury and are associated with the development of post-traumatic osteoarthritis (OA). The purpose of this study is to evaluate potential OA mediators in the synovial fluid and serum of meniscus tear subjects compar ... Full text Link to item Cite

Advances in combining gene therapy with cell and tissue engineering-based approaches to enhance healing of the meniscus.

Journal Article Osteoarthritis Cartilage · August 2016 Meniscal lesions are common problems in orthopaedic surgery and sports medicine, and injury or loss of the meniscus accelerates the onset of knee osteoarthritis (OA). Despite a variety of therapeutic options in the clinics, there is a critical need for imp ... Full text Link to item Cite

Cartilage-Specific Knockout of the Mechanosensory Ion Channel TRPV4 Decreases Age-Related Osteoarthritis.

Journal Article Sci Rep · July 8, 2016 Osteoarthritis (OA) is a progressive degenerative disease of articular cartilage and surrounding tissues, and is associated with both advanced age and joint injury. Biomechanical factors play a critical role in the onset and progression of OA, yet the mech ... Full text Link to item Cite

Mechanobiology of the meniscus.

Journal Article J Biomech · June 1, 2015 The meniscus plays a critical biomechanical role in the knee, providing load support, joint stability, and congruity. Importantly, growing evidence indicates that the mechanobiologic response of meniscal cells plays a critical role in the physiologic, path ... Full text Open Access Link to item Cite

In vivo cartilage strain increases following medial meniscal tear and correlates with synovial fluid matrix metalloproteinase activity.

Journal Article J Biomech · June 1, 2015 Meniscal tears are common injuries, and while partial meniscectomy is a frequent treatment option, general meniscus loss is a risk factor for the development of osteoarthritis. The goal of this study was to measure the in vivo tibiofemoral cartilage contac ... Full text Open Access Link to item Cite

TRPV4 as a therapeutic target for joint diseases.

Journal Article Naunyn Schmiedebergs Arch Pharmacol · April 2015 Biomechanical factors play a critical role in regulating the physiology as well as the pathology of multiple joint tissues and have been implicated in the pathogenesis of osteoarthritis. Therefore, the mechanisms by which cells sense and respond to mechani ... Full text Link to item Cite

Synergy between Piezo1 and Piezo2 channels confers high-strain mechanosensitivity to articular cartilage.

Journal Article Proc Natl Acad Sci U S A · November 25, 2014 Diarthrodial joints are essential for load bearing and locomotion. Physiologically, articular cartilage sustains millions of cycles of mechanical loading. Chondrocytes, the cells in cartilage, regulate their metabolic activities in response to mechanical l ... Full text Open Access Link to item Cite

The mechanobiology of articular cartilage: bearing the burden of osteoarthritis.

Journal Article Curr Rheumatol Rep · October 2014 Articular cartilage injuries and degenerative joint diseases are responsible for progressive pain and disability in millions of people worldwide, yet there is currently no treatment available to restore full joint functionality. As the tissue functions und ... Full text Link to item Cite

Follistatin in chondrocytes: the link between TRPV4 channelopathies and skeletal malformations.

Journal Article FASEB J · June 2014 Point mutations in the calcium-permeable TRPV4 ion channel have been identified as the cause of autosomal-dominant human motor neuropathies, arthropathies, and skeletal malformations of varying severity. The objective of this study was to determine the mec ... Full text Link to item Cite

Unraveling the mechanism by which TRPV4 mutations cause skeletal dysplasias.

Journal Article Rare Dis · 2014 Transient Receptor Potential Vanilloid 4 (TRPV4) is a mechano- and osmosensitive cation channel that is highly expressed in chondrocytes, the cells in cartilage. A large number of mutations in TRPV4 have been linked to skeletal dysplasias, and the goal of ... Full text Link to item Cite

Temporomandibular joint pain: a critical role for Trpv4 in the trigeminal ganglion.

Journal Article Pain · August 2013 Temporomandibular joint disorder (TMJD) is known for its mastication-associated pain. TMJD is medically relevant because of its prevalence, severity, chronicity, the therapy-refractoriness of its pain, and its largely elusive pathogenesis. Against this bac ... Full text Open Access Link to item Cite

Synovial fluid concentrations and relative potency of interleukin-1 alpha and beta in cartilage and meniscus degradation.

Journal Article J Orthop Res · July 2013 Cartilage degeneration with osteoarthritis (OA) is believed to involve the activities of interleukin-1 (IL-1), which exists as alpha and beta isoforms. The goal of this study was to measure the concentrations of both isoforms of IL-1 in the synovial fluid ... Full text Link to item Cite

Cartilage viability and catabolism in the intact porcine knee following transarticular impact loading with and without articular fracture.

Journal Article J Orthop Res · April 2011 Posttraumatic arthritis commonly develops following articular fracture. The objective of this study was to develop a closed joint model of transarticular impact with and without creation of an articular fracture that maintains the physiologic environment d ... Full text Link to item Cite

The effects of adipokines on cartilage and meniscus catabolism.

Journal Article Connect Tissue Res · 2011 Obesity is one of the primary risk factors for osteoarthritis. Increased adiposity is associated not only with alterations in joint loading, but also with increased systemic and joint concentrations of adipose tissue-derived cytokines, or "adipokines", tha ... Full text Link to item Cite

Interleukin-1, tumor necrosis factor-alpha, and transforming growth factor-beta 1 and integrative meniscal repair: influences on meniscal cell proliferation and migration.

Journal Article Arthritis Res Ther · 2011 INTRODUCTION: Interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) are up-regulated in injured and osteoarthritic knee joints. IL-1 and TNF-α inhibit integrative meniscal repair; however, the mechanisms by which this inhibition occurs are not fully und ... Full text Link to item Cite

Dynamic loading enhances integrative meniscal repair in the presence of interleukin-1.

Journal Article Osteoarthritis Cartilage · June 2010 OBJECTIVE: Meniscal tears are a common knee injury and increased levels of interleukin-1 (IL-1) have been measured in injured and degenerated joints. Studies have shown that IL-1 decreases the shear strength, cell accumulation, and tissue formation in meni ... Full text Link to item Cite

Inhibition of matrix metalloproteinases enhances in vitro repair of the meniscus.

Journal Article Clin Orthop Relat Res · June 2009 Damage or injury of the meniscus is associated with onset and progression of knee osteoarthritis (OA). The intrinsic repair capacity of the meniscus is inhibited by inflammatory cytokines, such as interleukin-1 (IL-1). Using an in vitro meniscal repair mod ... Full text Link to item Cite

Inhibition of integrative repair of the meniscus following acute exposure to interleukin-1 in vitro.

Journal Article J Orthop Res · April 2008 Damage or loss of the meniscus is associated with progressive osteoarthritic degeneration of the knee joint. Injured and degenerative joints are characterized by elevated levels of the pro-inflammatory cytokine interleukin-1 (IL-1), which with prolonged ex ... Full text Link to item Cite

Integrative repair of the meniscus: lessons from in vitro studies.

Journal Article Biorheology · 2008 Current therapies for meniscal injury seek to preserve and repair damaged tissue since loss of meniscal tissue is associated with degenerative changes in the joint, ultimately leading to osteoarthritis (OA). After a meniscal tear, the difficulty of integra ... Link to item Cite

Enhanced integrative repair of the porcine meniscus in vitro by inhibition of interleukin-1 or tumor necrosis factor alpha.

Journal Article Arthritis Rheum · September 2007 OBJECTIVE: To examine the hypotheses that increasing concentrations of interleukin-1 (IL-1) or tumor necrosis factor alpha (TNFalpha) inhibit the integrative repair of the knee meniscus in an in vitro model system, and that inhibitors of these cytokines wi ... Full text Link to item Cite

The effects of pro-inflammatory cytokines on functional repair of the meniscus

Journal Article MCB Molecular and Cellular Biomechanics · January 1, 2006 A study was performed to examine the hypotheses that increasing concentrations of the pro-inflammatory cytokines interleukin-1 (IL-1) or tumor necrosis factor-alpha (TNF) inhibit integrative repair of the knee meniscus in an in vitro model system and that ... Full text Cite

Dehydroascorbate transport in human chondrocytes is regulated by hypoxia and is a physiologically relevant source of ascorbic acid in the joint.

Journal Article Arthritis Rheum · September 2005 OBJECTIVE: To evaluate the dehydroascorbate (DHA) transport mechanisms in human chondrocytes. METHODS: The transport of L-(14)C-DHA in human chondrocytes was analyzed under various conditions, including the use of RNA interference (RNAi), to determine the ... Full text Link to item Cite

Chondrocyte transport and concentration of ascorbic acid is mediated by SVCT2.

Journal Article Biochim Biophys Acta · June 30, 2005 Collagen II is the major protein component of articular cartilage and forms the collagen fibril network, which provides the tensile strength of cartilage. Collagen II synthesis is enhanced by ascorbic acid (vitamin C) at both a transcriptional and post-tra ... Full text Link to item Cite

The effects of ascorbic acid on cartilage metabolism in guinea pig articular cartilage explants.

Journal Article Matrix Biol · March 2002 Ascorbic acid has been associated with the slowing of osteoarthritis progression in guinea pig and man. The goal of this study was to evaluate transcriptional and translational regulation of cartilage matrix components by ascorbic acid. Guinea pig articula ... Full text Link to item Cite

The role of CCR5 and CCR2 polymorphisms in HIV-1 transmission and disease progression.

Journal Article Nat Med · October 1997 Entry of human immunodeficiency virus type 1 (HIV-1) into target cells requires both CD4 (ref. 1, 2) and one of a growing number of G-protein-coupled seven-transmembrane receptors. Viruses predominantly use one, or occasionally both, of the major co-recept ... Full text Link to item Cite