Biology subjects

Brooks, S. V.

Publications and source records attributed to Brooks, S. V..

16 recordsLinked to original sources

bioRxiv2025

Histopathology and spatial transcriptomics jointly map myofiber-specific pathological programs in mTORC1-driven myopathy

Skeletal muscle is a structurally organized and functionally diverse organ composed of heterogeneous myofiber types and supporting non-myocyte populations that act in concert to generate force, regulate metabolism, and maintain systemic homeostasis. Myopathies occur in many different diseases, but the mechanisms that drive these muscle pathologies are still largely unknown, partly because conventional approaches cannot link histopathological features to molecular states at single-fiber resolution. To address this challenge, we brought histopathology and spatial transcriptomics together by applying high-resolution Seq-Scope technology to a rodent model of mTORC1 hyperactivation, which produces diverse pathological alterations within individual myofibers. Cross-sections from extensor digitorum longus (EDL) and soleus (SOL), two muscles with distinct fiber-type compositions, were profiled to determine how transcriptome changes are linked to histopathological outcomes. Our analyses reveal that mTORC1 hyperactivation elicits distinct, fiber-type-dependent pathological programs. Type I and IIa fibers, abundant in SOL but scarce in EDL, were largely resistant to mTORC1-induced pathology, exhibiting only minimal morphological alterations and no fiber type-specific responses beyond those commonly observed throughout the tissue. In contrast, type IIx fibers, shared between both muscles, diverged into opposing fates: in SOL, they underwent abnormal enlargement driven by sustained growth signaling, cytoskeletal remodeling, and impaired proteostasis with defective autophagy; whereas in EDL, they developed basophilia characterized by lipid-supported respiration fueling excessive ribonucleotide synthesis and RNA accumulation. Within the same muscle, type IIb fibers displayed striking heterogeneity with discrete transcriptional states encompassing canonical stress responses, oxidative metabolic activation, and developmental reprogramming. In parallel, non-myocytic populations, including activated macrophages and fibroblasts, accumulated preferentially in SOL, forming a fibrotic microenvironment supporting inflammation, tissue remodeling and hypertrophy. Taken together, these findings reveal that sustained mTORC1 signaling disrupts muscle homeostasis through distinct metabolic and structural routes, directly linking histopathological phenotypes to their molecular states at single-fiber resolution.

pathology↗

bioRxiv2025

Leukocyte-type 12/15-lipoxygenase is essential for timely inflammation-resolution and effective tissue regeneration following skeletal muscle injury

Unlike traditional anti-inflammatory therapies which may interfere with musculoskeletal tissue repair, pharmacological administration of specialized pro-resolving lipid mediators (SPMs) can promote timely resolution of inflammation while stimulating skeletal muscle regeneration. Despite this, the potential role of endogenous inflammation-resolution circuits in skeletal muscle injury and repair remains unknown. Here, we investigated the effect of whole-body knockout of leukocyte-type 12/15-lipoxygenase (12/15-LOX) on acute inflammation and regeneration following skeletal muscle injury in mice. Prior to muscle injury, Alox15-/- mice displayed lower intramuscular concentrations of 12/15-LOX-derived lipid mediators than wild type (WT) mice, and this was associated with chronic low-grade muscle inflammation. Alox15-/- mice mounted an exaggerated acute immune response to sterile skeletal muscle injury which was associated with a local imbalance of pro-inflammatory vs. pro-resolving lipid mediators. During the regenerative phase, Alox15-/- mice displayed defects in myogenic gene expression, myofiber size, and myonuclear accretion. Mechanistically, bone marrow-derived macrophages (M[FE]) obtained from Alox15-/- mice produced less 12/15-LOX-derived lipid mediators and this was associated with impaired M2 polarization. Isolated myogenic progenitor cells also produced many LOX metabolites in response to long chain polyunsaturated fatty acid (LC-PUFA) supplementation, including bioactive SPMs. Alox15-/- myoblasts were both impaired in their ability to produce SPMs and were insensitive to the stimulatory effect of LC-PUFAs on in vitro myogenesis. These data show that the 12/15-LOX pathway is essential for timely resolution of acute inflammation and direct determination of myogenic progenitor cell fate following skeletal muscle injury.

developmental biology↗

bioRxiv2025

AMPK signaling is dysregulated in human tendinopathy and loss of AMPKα1 leads to cell, matrix and mechanical dysfunction in mouse Achilles tendon

Tendinopathy is a debilitating tendon disorder affecting millions of people, characterized by pain, swelling, and diminished biomechanical properties. While the precise mechanisms underlying tendon homeostasis remain unclear, metabolic regulation plays a critical role. In this study, we combine transcriptomic analysis of human tendinopathic samples with a conditional mouse model in which Prkaa1 (encoding AMPK1) is selectively deleted in tendon progenitors to elucidate the role of AMPK signaling in tendon homeostasis. RNA sequencing of diseased human tendons revealed downregulation of key metabolic genes, including several involved in the mitochondrial electron transport chain and AMPK signaling pathways, alongside an increase in markers associated with senescence and a secretory inflammatory profile. In parallel, mice with loss of Prkaa1 function exhibited normal postnatal development; however, by one month of age, tendons demonstrated widespread transcriptional alterations related to cell cycle regulation and ECM organization. By three months, AMPK1-deficient tendons showed significant reductions in mechanical strength and increased expression of senescence markers p21 and p16, progressing to prominent ectopic calcification with age. In vitro studies further confirmed that tendon fibroblasts lacking AMPK1 have altered ECM substrate adhesion profiles. Importantly, voluntary exercise partially rescued these deficits by enhancing ECM organization and reducing senescence marker expression. Collectively, our findings demonstrate that AMPK1 is critical for maintaining energy balance, regulating ECM remodeling, and preventing premature cellular senescence in tendon. These insights highlight AMPK signaling as a promising therapeutic target and underscore the beneficial role of exercise in mitigating tendinopathic changes.

pathology↗

bioRxiv2024

Overexpression of enhanced yellow fluorescent protein fused with Channelrhodopsin-2 causes contractile dysfunction in skeletal muscle

Skeletal muscle activation using optogenetics has emerged as a promising technique for inducing noninvasive muscle contraction and assessing muscle function both in vivo and in vitro. Transgenic mice overexpressing the optogenetic fusion protein, Channelphodopsin2-EYFP (ChR2-EYFP) in skeletal muscle are widely used; however, overexpression of fluorescent proteins can negatively impact the functionality of activable tissues. In this study, we characterized the contractile properties of ChR2-EYFP skeletal muscle and introduced the ChR2-only mouse model that expresses light-responsive ChR2 without the fluorescent EYFP in their skeletal muscles. We found a significant reduction in the contractile ability of ChR2-EYFP muscles compared to ChR2-only and WT mice, observed under both electrical and optogenetic stimulation paradigms. Bulk RNAseq identified downregulation of genes associated with transmembrane transport and metabolism in ChR2-EYFP muscle, while the ChR2-only muscle did not demonstrate any notable deviations from WT muscle. The RNAseq results were further corroborated by a reduced protein-level expression of ion-channel-related HCN2 in ChR2-EYFP muscles and gluconeogenesis-modulating FBP2 in both ChR2-EYFP and ChR2-only muscles. Overall, this study reveals an intrinsic skeletal dysfunction in the widely used ChR2-EYFP mice model and underscores the importance of considering alternative optogenetic models, such as the ChR2-only, for future research in skeletal muscle optogenetics.

physiology↗

bioRxiv2023

Decoding muscle-resident Schwann cell dynamics during neuromuscular junction remodeling

This investigation leverages single-cell RNA sequencing (scRNA-Seq) to delineate the contributions of muscle-resident Schwann cells to neuromuscular junction (NMJ) remodeling by comparing a model of stable innervation with models of reinnervation following partial or complete denervation. The study discovered multiple distinct Schwann cell subtypes, including a novel terminal Schwann cell (tSC) subtype integral to the denervation-reinnervation cycle, identified by a transcriptomic signature indicative of cell migration and polarization. The data also characterizes three myelin Schwann cell subtypes, which are distinguished based on enrichment of genes associated with myelin production, mesenchymal differentiation or collagen synthesis. Importantly, SPP1 signaling emerges as a pivotal regulator of NMJ dynamics, promoting Schwann cell proliferation and muscle reinnervation across nerve injury models. These findings advance our understanding of NMJ maintenance and regeneration and underscore the therapeutic potential of targeting specific molecular pathways to treat neuromuscular and neurodegenerative disorders.

neuroscience↗

bioRxiv2023

Thrombospondin-1 promotes fibro-adipogenic stromal expansion and contractile dysfunction of the diaphragm in obesity

Pulmonary disorders impact 40-80% of individuals with obesity. Respiratory muscle dysfunction is linked to these conditions; however, its pathophysiology remains largely undefined. Mice subjected to diet-induced obesity (DIO) develop diaphragmatic weakness. Increased intra-diaphragmatic adiposity and extracellular matrix (ECM) content correlate with reductions in contractile force. Thrombospondin-1 (THBS1) is an obesity-associated matricellular protein linked with muscular damage in genetic myopathies. THBS1 induces proliferation of fibro-adipogenic progenitors (FAPs)--mesenchymal cells that differentiate into adipocytes and fibroblasts. We hypothesized that THBS1 drives FAP-mediated diaphragm remodeling and contractile dysfunction in DIO. We tested this by comparing effects of dietary challenge on diaphragms of wild-type (WT) and Thbs1 knockout (Thbs1-/-) mice. Bulk and single-cell transcriptomics demonstrated DIO-induced stromal expansion in WT diaphragms. Diaphragm FAPs displayed upregulation of ECM and TGF{beta}-related expression signatures, and augmentation of a Thy1-expressing sub-population previously linked to type 2 diabetes. Despite similar weight gain, Thbs1-/- mice were protected from these transcriptomic changes, and from obesity-induced increases in diaphragm adiposity and ECM deposition. Unlike WT controls, Thbs1-/-diaphragms maintained normal contractile force and motion after DIO challenge. These findings establish THBS1 as a necessary mediator of diaphragm stromal remodeling and contractile dysfunction in overnutrition, and potential therapeutic target in obesity-associated respiratory dysfunction.

cell biology↗

bioRxiv2022

Maresin 1 Repletion Improves Muscle Regeneration After Volumetric Muscle Loss

The acute traumatic or surgical loss of skeletal muscle, known as volumetric muscle loss (VML), is a devastating type of injury that results in exacerbated and persistent inflammation followed by fibrosis. The mechanisms that mediate the magnitude and duration of the inflammatory response and ensuing fibrosis after VML remain understudied and as such, the development of regenerative therapies has been limited. To address this need, we profiled how lipid mediators, which are potent regulators of the immune response after injury, varied with VML injuries that heal or result in fibrosis. We observed that non-healing VML injuries displayed increased pro-inflammatory eicosanoids and a lack of pro-resolving lipid mediators. Treatment of VML with a pro-resolving lipid mediator synthesized from docosahexaenoic acid, called Maresin 1, ameliorated fibrosis through reduction of neutrophils and macrophages and improved myogenesis, leading to enhanced recovery of muscle strength. These results expand our knowledge of the dysregulated immune response that develops after VML and identify a novel immuno-regenerative therapeutic modality in Maresin 1.

physiology↗

bioRxiv2022

Deletion of Sod1 in motor neurons exacerbates age-related changes in axons and NMJs associated with premature muscle atrophy in aging mice

Whole body knock out of Cu, Zn superoxide dismutase1 (Sod1KO) results in accelerated, age-related loss of muscle mass and function associated with a breakdown of neuromuscular junctions (NMJ) similar to sarcopenia. In order to determine whether altered redox in motor neurons is integral to this phenotype, an inducible neuron specific deletion of Sod1 (i-mnSod1KO) was compared with wild type (WT) mice of different ages (adult, mid-age and old) and whole body Sod1KO mice. Nerve oxidative damage, motor neuron numbers and structural changes to neurons and NMJ were examined. Deletion of neuronal Sod1 (induced by tamoxifen injection at 6 months of age) caused the exaggerated, age-associated loss of muscle mass and force generation previously reported. No effect of age or lack of neuronal Sod1 was seen on oxidation in the sciatic nerve assessed by electron paramagnetic resonance of the in vivo spin probe 1-hydroxy-3-carboxy-2,2,5,5 tetramethylpyrrolidine (CPH), analysis of protein 3-nitrotyrosines or carbonyl content. i-mnSod1KO mice showed increased numbers of denervated NMJs, a reduced number of large axons and increased number of small axons compared with age-matched old WT mice. A large proportion of the remaining innervated NMJs in i-mnSod1KO mice also displayed a much simpler structure than that seen in WT mice. Thus, while Sod1KO mice recapitulate substantially the neuromuscular phenotypes of old WT mice, deletion of Sod1 specifically in neurons induces exaggerated loss of muscle mass and force only in old (24-29 month) mice indicating that significant muscle declines require the accumulation of age-related changes such that a threshold is reached past which maintenance of structure and function is not possible. Significance statementSarcopenia is the age-related loss of muscle mass and function. It is a significant contributor to frailty and to increased falls in the elderly. While multifactorial, changes in redox status have been shown to have significant influence over neuromuscular aging, recent work suggests that changes in motor neurons may be the driving factor in muscle atrophy. The current study confirmed that a specific lack of Sod1 in the motor neuron causes significant alteration in axonal architecture and the neuromuscular junctions which can drive reduced muscle mass and function. Pinpointing early changes in motor neurons may provide therapeutic targets critical for maintaining muscle in the elderly.

physiology↗

bioRxiv2021

Neutrophil and natural killer cell imbalances prevent muscle stem cell mediated regeneration following murine volumetric muscle loss

Volumetric muscle loss (VML) overwhelms the innate regenerative capacity of mammalian skeletal muscle (SkM), leading to numerous disabilities and reduced quality of life. Immune cells are critical responders to muscle injury and guide tissue resident stem cell and progenitor mediated myogenic repair. However, how immune cell infiltration and inter-cellular communication networks with muscle stem cells are altered following VML and drive pathological outcomes remains underexplored. Herein, we contrast the cellular and molecular mechanisms of VML injuries that result in fibrotic degeneration or regeneration of SkM. Following degenerative VML injuries, we observe heightened infiltration of natural killer (NK) cells as well as persistence of neutrophils beyond two weeks post injury. Functional validation of NK cells revealed an antagonistic role on neutrophil accumulation in part via inducing apoptosis and CCR1 mediated chemotaxis. The persistent infiltration of neutrophils in degenerative VML injuries was found to contribute to impairments in muscle stem cell regenerative function, which was also attenuated by transforming growth factor beta 1 (TGF{beta}1). Blocking TGF{beta} signaling reduced neutrophil accumulation and fibrosis, as well as improved muscle specific force. Collectively, these results enhance our understanding of immune cell-stem cell crosstalk that drives regenerative dysfunction and provide further insight into possible avenues for fibrotic therapy exploration. SINGLE SENTENCE SUMMARYComparison of muscle injuries resulting in regeneration or fibrosis reveals inter-cellular communication between neutrophils and natural killer cells impacts muscle stem cell mediated repair.

cell biology↗

bioRxiv2021

Local Shifts in Inflammatory and Resolving Lipid Mediators in Response to Tendon Overuse

Tendon inflammation has been implicated in both adaptive connective tissue remodeling and overuse-induced tendinopathy. Lipid mediators control the initiation and resolution of inflammation, but their roles within tendon are largely unknown. Here we profiled local shifts in intratendinous lipid mediators via liquid chromatography-tandem mass spectrometry in response to synergist ablation-induced plantaris tendon overuse. Sixty-four individual lipid mediators were detected in homogenates of habitually loaded plantaris tendons from healthy ambulatory rats. This included many bioactive metabolites of the cyclooxygenase (COX), lipoxygenase (LOX), and epoxygenase (CYP) pathways. Synergist ablation induced a robust inflammatory response at day 3 post-surgery characterized by epitenon infiltration of polymorphonuclear leukocytes (PMNs) and macrophages (M{Phi}), heightened expression of inflammation-related genes, and increased intratendinous concentrations of the pro-inflammatory eicosanoids thromboxane B2 (TXB2) and prostaglandin E2 (PGE2). By day 7, M{Phi} became the predominant myeloid cell type in tendon and there were further delayed increases in other COX metabolites including PGD2, PGF2 and PGI2. Specialized pro-resolving mediators (SPMs) including protectin D1 (PD1) and resolvin D6 (RvD6), as well as related pathway markers of D-resolvins (17-HDoHE), E-resolvins (18-HEPE) and lipoxins (15-HETE) were also increased locally in response to tendon overuse, as were many anti-inflammatory fatty acid epoxides of the CYP pathway (e.g. EpETrEs). Nevertheless, intratendinous prostaglandins remained markedly increased even following 28 days of tendon overuse together with a lingering M{Phi} presence. These data reveal a delayed and prolonged local inflammatory response to tendon overuse characterized by an overwhelming predominance of pro-inflammatory eicosanoids and a relative lack of pro-resolving lipid mediators.

immunology↗

bioRxiv2020

Sestrins regulate age-induced deterioration of muscle stem cell homeostasis

The health and homeostasis of skeletal muscle is preserved by a population of tissue resident stem cells called satellite cells. Young healthy satellite cells maintain a state of quiescence, but aging or metabolic insults results in reduced capacity to prevent premature activation and stem cell exhaustion. As such, understanding genes and pathways that protect satellite cell maintenance of quiescence are needed. Sestrins are a class of stress-inducible proteins that act as antioxidants and inhibit the activation of the mammalian target of rapamycin complex 1 (mTORC1) signaling complex. Despite these pivotal roles, the role of Sestrins has not been explored in adult stem cells. Herein, we show that Sestrin1,2 loss results in hyperactivation of the mTORC1 complex, increased propensity to enter the cell cycle and shifts in metabolic flux. Aging of Sestrin1,2 knockout mice demonstrated a loss of MuSCs and reduced ability to regenerate. These findings demonstrate Sestrins function to help maintain MuSC metabolism that supports quiescence and against aging. HighlightsO_LISestrin deficiency alters mTORC1 signaling in muscle stem cells (MuSCs). C_LIO_LIIn young mice, Sestrins are dispensable for regenerative responses of MuSCs. C_LIO_LISestrin deficiency accelerates age-dependent loss and dysfunction of MuSCs. C_LI

cell biology↗

bioRxiv2020

Lipidomic Profiling Reveals an Age-Related Deficiency of Skeletal Muscle Proresolving Mediators that Contributes to Maladaptive Tissue Remodeling

Chronic inflammation and deregulated acute immune cell responses to injury contribute to age-associated skeletal muscle dysfunction. Specialized pro-resolving mediators (SPMs) control inflammation and support myofiber regeneration in young mice, but their role in aging muscle remains unknown. Here we examined the effect of age on the mediator lipidome of skeletal muscle via LC-MS based lipidomic profiling and tested whether systemic administration of the SPM resolvin D1 (RvD1) could limit excessive inflammation and improve the regenerative capacity of aged muscle. Aged mice displayed chronic low-grade muscle inflammation prior to injury and this was associated with a basal deficiency of lipoxygenase (LOX) derived SPMs as well as anti-inflammatory cytochrome P450 (CYP) derived lipid epoxides. Following muscle damage, young and aged mice produced similar amounts of pro-inflammatory cyclooxygenase (COX) and 12-LOX metabolites, but aged mice mounted a markedly deficient SPM response. This was associated with heightened leukocyte recruitment, impaired myofiber regeneration, and delayed recovery of strength. Systemic treatment with RvD1 had minimal impact on excessive myeloid cell infiltration and defective myofiber regeneration in aged mice. Nevertheless, RvD1 treatment did suppress inflammatory cytokines, modulated muscle stem cells, limited maladaptive tissue remodeling, and improved recovery of specific muscle force. We conclude that aging results in a marked deficiency of local SPM biosynthesis within muscle and that immunoresolvents may be attractive novel therapeutics for the treatment of muscular injuries and associated pain in the elderly, due to positive effects on recovery of muscle function without the negative side effects on myofiber regeneration of traditional anti-inflammatory treatments.

immunology↗

bioRxiv2020

Obesity promotes glucocorticoid-dependent muscle atrophy in male C57BL/6J mice.

Glucocorticoids promote muscle atrophy by inducing a class of proteins called atrogenes, resulting in reductions in muscle size and strength. In this work, we evaluated whether a mouse model with pre-existing diet-induced obesity had altered glucocorticoid responsiveness. We observed that all animals treated with the synthetic glucocorticoid dexamethasone had reduced strength, but that obesity exacerbated this effect. These changes were concordant with more pronounced reductions in muscle size, particularly in Type II muscle fibers, and potentiated induction of atrogene expression in the obese mice relative to lean mice. Furthermore, we show that the reductions in lean mass do not fully account for the dexamethasone-induced insulin resistance observed in these mice. Together these data suggest that obesity potentiates glucocorticoid-induced muscle atrophy.

physiology↗

bioRxiv2020

Immunoresolvents Support Skeletal Myofiber Regeneration via Actions on Myeloid and Muscle Stem Cells

Specialized pro-resolving mediators (SPMs) actively limit inflammation and expedite its resolution. Here we profiled intramuscular lipid mediators following injury and investigated the role of SPMs in skeletal muscle inflammation and repair. Both eicosanoids and SPMs increased following myofiber damage induced by intramuscular injection of barium chloride or functional overload. Daily systemic administration of resolvin D1 (RvD1) limited the degree and duration of inflammation, enhanced regenerating myofiber growth, and improved recovery of muscle strength. RvD1 suppressed inflammatory cytokines, enhanced polymorphonuclear cell clearance, modulated muscle stem cells, and polarized macrophages to a more pro-regenerative subset. RvD1 had minimal direct impact on in-vitro myogenesis but directly suppressed myokine production and stimulated macrophage phagocytosis, showing that SPMs influence modulate both infiltrating myeloid and resident muscle cells. These data reveal the efficacy of immunoresolvents as a novel alternative to classical anti-inflammatory interventions in the management of muscle injuries to modulate inflammation while stimulating tissue repair.

immunology↗

bioRxiv2020

Single Cell Deconstruction of Muscle Stem Cell Heterogeneity During Aging Reveals Sensitivity to the Neuromuscular Junction

During aging and neuromuscular diseases, there is a progressive loss of skeletal muscle volume and function in that impacts mobility and quality of life. Muscle loss is often associated with denervation and a loss of resident muscle stem cells (satellite cells or MuSCs), but the relationship between MuSCs and neural control has not been established. Herein, using a combination of single-cell transcriptomic analysis, high-resolution immunofluorescence imaging and transgenic young and aged mice as well as from mice with neuromuscular degeneration (Sod1-/-), a compensatory neuro-responsive function for a subset of MuSCs was identified. Genetic rescue of motor neurons in Sod1-/- mice reduced this subset of MuSCs and restored integrity of the neuromuscular junction (NMJ) in a manner akin to young muscle. Administration of severe neuromuscular trauma induced young MuSCs to specifically engraft in a position proximal to the NMJ but in aging, this behavior was abolished. Contrasting the expression programs of young and aged MuSCs after muscle injury at the single cell level, we observed distinctive gene expression programs between responses to neuro-muscular degeneration and muscle trauma. Collectively, these data reveal MuSCs sense synaptic perturbations during aging and neuro-muscular deterioration, and can exert support for the NMJ, particularly in young muscle. HighlightsO_LITranscriptional landscapes of single satellite cells from different ages before and after injury as well as neurodegenerative models before and after nervous rescue C_LIO_LIA population of satellite cells reside in close proximity to neuromuscular synapse, which are lost with age C_LIO_LIDenervation promotes satellite cell engraftment into post-synaptic regions of young as opposed to aged muscle C_LI

cell biology↗

bioRxiv2017

Postnatal Tendon Growth and Remodeling Requires Platelet-Derived Growth Factor Receptor Signaling

Platelet-derived growth factor receptor (PDGFR) signaling plays an important role in the fundamental biological activities of many cells that compose musculoskeletal tissues. However, little is known about the role of PDGFR signaling during tendon growth and remodeling in adult animals. Using the hindlimb synergist ablation model of tendon growth, our objectives were to determine the role of PDGFR signaling in the adaptation of tendons subjected to a mechanical growth stimulus, as well as to investigate the biological mechanisms behind this response. We demonstrate that both PDGFRs, PDGFR and PDGFR{beta}, are expressed in tendon fibroblasts, and that the inhibition of PDGFR signaling suppresses the normal growth of tendon tissue in response to mechanical growth cues due to defects in fibroblast proliferation and migration. We also identify that membrane type-1 matrix metalloproteinase (MT1-MMP) as an essential proteinase for the migration of tendon fibroblasts through their extracellular matrix. Furthermore, we report that MT1-MMP translation is regulated by PI3K/Akt signaling, while ERK1/2 controls post-translational trafficking of MT1-MMP to the plasma membrane of tendon fibroblasts. Taken together, these findings demonstrate that PDGFR signaling is necessary for postnatal tendon growth and remodeling, and that MT1-MMP is a critical mediator of tendon fibroblast migration and a potential target for the treatment of tendon injuries and diseases.

physiology↗