Scholars@Duke
Gurpreet Baht

Gurpreet Baht

Associate Professor in Orthopaedic Surgery
Orthopaedic Surgery
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Selected Publications

Vagus nerve stimulation rescues persistent pain following orthopedic surgery in adult mice.

Conference Pain · August 1, 2024 Postoperative pain is a major clinical problem imposing a significant burden on patients and society. In a survey 2 years after orthopedic surgery, 57% of patients reported persisting postoperative pain. However, only limited progress has been made in the ... Full text Link to item Cite

Osteoimmunology of Fracture Healing.

Journal Article Curr Osteoporos Rep · June 2024 PURPOSE OF REVIEW: The purpose of this review is to summarize what is known in the literature about the role inflammation plays during bone fracture healing. Bone fracture healing progresses through four distinct yet overlapping phases: formation of the he ... Full text Link to item Cite

The impact of age and sex on the inflammatory response during bone fracture healing.

Journal Article JBMR Plus · May 2024 Inflammation is thought to be dysregulated with age leading to impaired bone fracture healing. However, broad analyses of inflammatory processes during homeostatic bone aging and during repair are lacking. Here, we assessed changes in inflammatory cell and ... Full text Link to item Cite

Liver-derived plasminogen mediates muscle stem cell expansion during caloric restriction through the plasminogen receptor Plg-RKT.

Journal Article Cell Rep · March 26, 2024 An intriguing effect of short-term caloric restriction (CR) is the expansion of certain stem cell populations, including muscle stem cells (satellite cells), which facilitate an accelerated regenerative program after injury. Here, we utilized the MetRSL274 ... Full text Link to item Cite

Multi-omic rejuvenation and life span extension on exposure to youthful circulation

Journal Article Nature Aging · August 1, 2023 Heterochronic parabiosis (HPB) is known for its functional rejuvenation effects across several mouse tissues. However, its impact on biological age and long-term health is unknown. Here we performed extended (3-month) HPB, followed by a 2-month detachment ... Full text Cite

Biological age is increased by stress and restored upon recovery.

Journal Article Cell Metab · May 2, 2023 Aging is classically conceptualized as an ever-increasing trajectory of damage accumulation and loss of function, leading to increases in morbidity and mortality. However, recent in vitro studies have raised the possibility of age reversal. Here, we report ... Full text Link to item Cite

An enhancer-based gene-therapy strategy for spatiotemporal control of cargoes during tissue repair.

Journal Article Cell stem cell · January 2023 The efficacy and safety of gene-therapy strategies for indications like tissue damage hinge on precision; yet, current methods afford little spatial or temporal control of payload delivery. Here, we find that tissue-regeneration enhancer elements (TREEs) i ... Full text Cite

Meteorin-like is an injectable peptide that can enhance regeneration in aged muscle through immune-driven fibro/adipogenic progenitor signaling.

Journal Article Nat Commun · December 9, 2022 Pathologies associated with sarcopenia include decline in muscular strength, lean mass and regenerative capacity. Despite the substantial impact on quality of life, no pharmacological therapeutics are available to counteract the age-associated decline in f ... Full text Link to item Cite

The role of Meteorin-like in skeletal development and bone fracture healing.

Journal Article J Orthop Res · November 2022 Meteorin-like protein (Metrnl), homologous to the initially identified neurotrophic factor Meteorin, is a secreted, multifunctional protein. Here we used mouse models to investigate Metrnl's role in skeletal development and bone fracture healing. During de ... Full text Link to item Cite

Rejuvenation of neutrophils and their extracellular vesicles is associated with enhanced aged fracture healing.

Journal Article Aging Cell · July 2022 Tissue repair is negatively affected by advanced age. Recent evidence indicates that hematopoietic cell-derived extracellular vesicles (EVs) are modulators of regenerative capacity. Here, we report that plasma EVs carrying specific surface markers indicate ... Full text Link to item Cite

Parabiosis: Assessing the Effects of Circulating Cells and Factors on the Skeleton.

Chapter · 2021 The circulatory system carries within it numerous types of cells, proteins, and other factors that are able to influence the local biology of tissues. Within this chapter, we present a protocol for parabiosis, a surgical model which results in shared circu ... Full text Link to item Cite

APOLIPOPROTEIN E IMPAIRS AGED BONE FRACTURE HEALING

Conference INNOVATION IN AGING · 2021 Cite

Maresin 1 resolves aged-associated macrophage inflammation to improve bone regeneration.

Journal Article FASEB J · October 2020 Inflammaging is associated with poor tissue regeneration observed in advanced age. Specifically, protracted inflammation after acute injury has been associated with decreased bone fracture healing and increased rates of nonunion in elderly patients. Here, ... Full text Link to item Cite

Author Correction: Meteorin-like facilitates skeletal muscle repair through a Stat3/IGF-1 mechanism.

Journal Article Nat Metab · August 2020 An amendment to this paper has been published and can be accessed via a link at the top of the paper. ... Full text Link to item Cite

Meteorin-like facilitates skeletal muscle repair through a Stat3/IGF-1 mechanism.

Journal Article Nat Metab · March 2020 The immune system plays a multifunctional role throughout the regenerative process, regulating both pro-/anti-inflammatory phases and progenitor cell function. In the present study, we identify the myokine/cytokine Meteorin-like (Metrnl) as a critical regu ... Full text Link to item Cite

In Vivo Sequestration of Innate Small Molecules to Promote Bone Healing.

Journal Article Adv Mater · February 2020 Approaches that enable innate repair mechanisms hold great potential for tissue repair. Herein, biomaterial-assisted sequestration of small molecules is described to localize pro-regenerative signaling at the injury site. Specifically, a synthetic biomater ... Full text Link to item Cite

Maresin 1 resolves macrophage inflammation to improve aged bone fracture healing

Conference JOURNAL OF BONE AND MINERAL RESEARCH · 2020 Cite

The broad spectrum mixed-lineage kinase 3 inhibitor URMC-099 prevents acute microgliosis and cognitive decline in a mouse model of perioperative neurocognitive disorders.

Journal Article J Neuroinflammation · October 28, 2019 BACKGROUND: Patients with pre-existing neurodegenerative disease commonly experience fractures that require orthopedic surgery. Perioperative neurocognitive disorders (PND), including delirium and postoperative cognitive dysfunction, are serious complicati ... Full text Link to item Cite

Vagus nerve stimulation rescues persistent pain following orthopedic surgery in adult mice.

Conference Pain · August 1, 2024 Postoperative pain is a major clinical problem imposing a significant burden on patients and society. In a survey 2 years after orthopedic surgery, 57% of patients reported persisting postoperative pain. However, only limited progress has been made in the ... Full text Link to item Cite

Osteoimmunology of Fracture Healing.

Journal Article Curr Osteoporos Rep · June 2024 PURPOSE OF REVIEW: The purpose of this review is to summarize what is known in the literature about the role inflammation plays during bone fracture healing. Bone fracture healing progresses through four distinct yet overlapping phases: formation of the he ... Full text Link to item Cite

The impact of age and sex on the inflammatory response during bone fracture healing.

Journal Article JBMR Plus · May 2024 Inflammation is thought to be dysregulated with age leading to impaired bone fracture healing. However, broad analyses of inflammatory processes during homeostatic bone aging and during repair are lacking. Here, we assessed changes in inflammatory cell and ... Full text Link to item Cite

Liver-derived plasminogen mediates muscle stem cell expansion during caloric restriction through the plasminogen receptor Plg-RKT.

Journal Article Cell Rep · March 26, 2024 An intriguing effect of short-term caloric restriction (CR) is the expansion of certain stem cell populations, including muscle stem cells (satellite cells), which facilitate an accelerated regenerative program after injury. Here, we utilized the MetRSL274 ... Full text Link to item Cite

Multi-omic rejuvenation and life span extension on exposure to youthful circulation

Journal Article Nature Aging · August 1, 2023 Heterochronic parabiosis (HPB) is known for its functional rejuvenation effects across several mouse tissues. However, its impact on biological age and long-term health is unknown. Here we performed extended (3-month) HPB, followed by a 2-month detachment ... Full text Cite

Biological age is increased by stress and restored upon recovery.

Journal Article Cell Metab · May 2, 2023 Aging is classically conceptualized as an ever-increasing trajectory of damage accumulation and loss of function, leading to increases in morbidity and mortality. However, recent in vitro studies have raised the possibility of age reversal. Here, we report ... Full text Link to item Cite

An enhancer-based gene-therapy strategy for spatiotemporal control of cargoes during tissue repair.

Journal Article Cell stem cell · January 2023 The efficacy and safety of gene-therapy strategies for indications like tissue damage hinge on precision; yet, current methods afford little spatial or temporal control of payload delivery. Here, we find that tissue-regeneration enhancer elements (TREEs) i ... Full text Cite

Meteorin-like is an injectable peptide that can enhance regeneration in aged muscle through immune-driven fibro/adipogenic progenitor signaling.

Journal Article Nat Commun · December 9, 2022 Pathologies associated with sarcopenia include decline in muscular strength, lean mass and regenerative capacity. Despite the substantial impact on quality of life, no pharmacological therapeutics are available to counteract the age-associated decline in f ... Full text Link to item Cite

The role of Meteorin-like in skeletal development and bone fracture healing.

Journal Article J Orthop Res · November 2022 Meteorin-like protein (Metrnl), homologous to the initially identified neurotrophic factor Meteorin, is a secreted, multifunctional protein. Here we used mouse models to investigate Metrnl's role in skeletal development and bone fracture healing. During de ... Full text Link to item Cite

Rejuvenation of neutrophils and their extracellular vesicles is associated with enhanced aged fracture healing.

Journal Article Aging Cell · July 2022 Tissue repair is negatively affected by advanced age. Recent evidence indicates that hematopoietic cell-derived extracellular vesicles (EVs) are modulators of regenerative capacity. Here, we report that plasma EVs carrying specific surface markers indicate ... Full text Link to item Cite

Parabiosis: Assessing the Effects of Circulating Cells and Factors on the Skeleton.

Chapter · 2021 The circulatory system carries within it numerous types of cells, proteins, and other factors that are able to influence the local biology of tissues. Within this chapter, we present a protocol for parabiosis, a surgical model which results in shared circu ... Full text Link to item Cite

APOLIPOPROTEIN E IMPAIRS AGED BONE FRACTURE HEALING

Conference INNOVATION IN AGING · 2021 Cite

Maresin 1 resolves aged-associated macrophage inflammation to improve bone regeneration.

Journal Article FASEB J · October 2020 Inflammaging is associated with poor tissue regeneration observed in advanced age. Specifically, protracted inflammation after acute injury has been associated with decreased bone fracture healing and increased rates of nonunion in elderly patients. Here, ... Full text Link to item Cite

Author Correction: Meteorin-like facilitates skeletal muscle repair through a Stat3/IGF-1 mechanism.

Journal Article Nat Metab · August 2020 An amendment to this paper has been published and can be accessed via a link at the top of the paper. ... Full text Link to item Cite

Meteorin-like facilitates skeletal muscle repair through a Stat3/IGF-1 mechanism.

Journal Article Nat Metab · March 2020 The immune system plays a multifunctional role throughout the regenerative process, regulating both pro-/anti-inflammatory phases and progenitor cell function. In the present study, we identify the myokine/cytokine Meteorin-like (Metrnl) as a critical regu ... Full text Link to item Cite

In Vivo Sequestration of Innate Small Molecules to Promote Bone Healing.

Journal Article Adv Mater · February 2020 Approaches that enable innate repair mechanisms hold great potential for tissue repair. Herein, biomaterial-assisted sequestration of small molecules is described to localize pro-regenerative signaling at the injury site. Specifically, a synthetic biomater ... Full text Link to item Cite

Maresin 1 resolves macrophage inflammation to improve aged bone fracture healing

Conference JOURNAL OF BONE AND MINERAL RESEARCH · 2020 Cite

The broad spectrum mixed-lineage kinase 3 inhibitor URMC-099 prevents acute microgliosis and cognitive decline in a mouse model of perioperative neurocognitive disorders.

Journal Article J Neuroinflammation · October 28, 2019 BACKGROUND: Patients with pre-existing neurodegenerative disease commonly experience fractures that require orthopedic surgery. Perioperative neurocognitive disorders (PND), including delirium and postoperative cognitive dysfunction, are serious complicati ... Full text Link to item Cite

Lowering circulating apolipoprotein E levels improves aged bone fracture healing.

Journal Article JCI Insight · September 19, 2019 Age is a well-established risk factor for impaired bone fracture healing. Here, we identify a role for apolipoprotein E (ApoE) in age-associated impairment of bone fracture healing and osteoblast differentiation, and we investigate the mechanism by which A ... Full text Link to item Cite

The broad spectrum mixed-lineage kinase 3 inhibitor URMC-099 prevents acute microgliosis and cognitive decline in a mouse model of perioperative neurocognitive disorders

Journal Article · February 2019 Abstract Perioperative neurocognitive disorders (PND), including delirium and postoperative cognitive dysfunction, are serious complications that afflict up to 50% of surgical patients and for which there are no disease-modifying therapeutic options. Here, ... Full text Cite

Macrophage cells secrete factors including LRP1 that orchestrate the rejuvenation of bone repair in mice.

Journal Article Nat Commun · December 5, 2018 The pace of repair declines with age and, while exposure to a young circulation can rejuvenate fracture repair, the cell types and factors responsible for rejuvenation are unknown. Here we report that young macrophage cells produce factors that promote ost ... Full text Open Access Link to item Cite

The role of apolipoprotein E in fracture healing and osteoblast differentiation

Conference JOURNAL OF BONE AND MINERAL RESEARCH · November 1, 2018 Link to item Cite

The Role of the Immune Cells in Fracture Healing.

Journal Article Curr Osteoporos Rep · April 2018 PURPOSE OF REVIEW: Bone fracture healing is a complex physiological process relying on numerous cell types and signals. Inflammatory factors secreted by immune cells help to control recruitment, proliferation, differentiation, and activation of hematopoiet ... Full text Link to item Cite

A Mouse Model of Orthopedic Surgery to Study Postoperative Cognitive Dysfunction and Tissue Regeneration.

Journal Article J Vis Exp · February 27, 2018 Surgery is commonly used to improve and maintain quality of life. Unfortunately, in vulnerable patients such as the elderly, complications may occur and significantly diminish the outcome. Indeed, after routine orthopedic surgery to repair a fracture, as m ... Full text Link to item Cite

A Role for Apolipoprotein E in Fracture Healing.

Conference JOURNAL OF BONE AND MINERAL RESEARCH · December 1, 2017 Link to item Cite

Pharmacologically targeting beta-catenin for NF1 associated deficiencies in fracture repair.

Journal Article Bone · May 2017 Patients with Neurofibromatosis type 1 display delayed fracture healing and the increased deposition of fibrous tissue at the fracture site. Severe cases can lead to non-union and even congenital pseudarthrosis. Neurofibromatosis type 1 is caused by a muta ... Full text Link to item Cite

Bone Marrow Stress Decreases Osteogenic Progenitors.

Journal Article Calcif Tissue Int · November 2015 Age-related bone loss may be a result of declining levels of stem cells in the bone marrow. Using the Col2.3Δtk (DTK) transgenic mouse, osteoblast depletion was used as a source of marrow stress in order to investigate the effects of aging on osteogenic pr ... Full text Link to item Cite

Macrophages promote osteoblastic differentiation in-vivo: implications in fracture repair and bone homeostasis.

Journal Article J Bone Miner Res · June 2015 Macrophages are activated in inflammation and during early phases of repair processes. Interestingly, they are also present in bone during development, but their function during this process is unclear. Here, we explore the function of macrophages in bone ... Full text Link to item Cite

Exposure to a youthful circulaton rejuvenates bone repair through modulation of β-catenin.

Journal Article Nat Commun · May 19, 2015 The capacity for tissues to repair and regenerate diminishes with age. We sought to determine the age-dependent contribution of native mesenchymal cells and circulating factors on in vivo bone repair. Here we show that exposure to youthful circulation by h ... Full text Link to item Cite

Activation of hedgehog signaling during fracture repair enhances osteoblastic-dependent matrix formation.

Journal Article J Orthop Res · April 2014 Fracture repair is a well orchestrated process involving various cell types and signaling molecules. The hedgehog signaling pathway is activated in chondrocytes during fracture repair and is known to regulate chondrogenesis however, its role in osteoblasts ... Full text Link to item Cite

Osteoblast depletion increases osteoblast activity and reduces bone toughness in mice.

Conference JOURNAL OF BONE AND MINERAL RESEARCH · February 1, 2014 Link to item Cite

Specification of chondrocytes and cartilage tissues from embryonic stem cells.

Journal Article Development · June 2013 Osteoarthritis primarily affects the articular cartilage of synovial joints. Cell and/or cartilage replacement is a promising therapy, provided there is access to appropriate tissue and sufficient numbers of articular chondrocytes. Embryonic stem cells (ES ... Full text Link to item Cite

Rejuvenating Bone Fracture Repair

Conference JOURNAL OF BONE AND MINERAL RESEARCH · February 1, 2013 Link to item Cite

Phosphorylation of Ser136 is critical for potent bone sialoprotein-mediated nucleation of hydroxyapatite crystals.

Journal Article Biochem J · May 27, 2010 Acidic phosphoproteins of mineralized tissues such as bone and dentin are believed to play important roles in HA (hydroxyapatite) nucleation and growth. BSP (bone sialoprotein) is the most potent known nucleator of HA, an activity that is thought to be dep ... Full text Link to item Cite

Bone repair mediated by bone sialoprotein

Conference European Cells and Materials · December 1, 2008 Cite

Bone sialoprotein-collagen interaction promotes hydroxyapatite nucleation.

Journal Article Matrix Biol · September 2008 In bone, hydroxyapatite (HA) crystals are deposited onto the type I collagen scaffold by a mechanism that has yet to be elucidated. Bone sialoprotein (BSP) is an acidic phosphoprotein that is expressed at high levels in mineralized tissues, capable of bind ... Full text Link to item Cite