Sex differences in tendon structure and function

Tendons play a critical role in the transmission of forces between muscles and bones, and chronic tendon injuries and diseases are among the leading causes of musculoskeletal disability. Little is known about sex‐based differences in tendon structure and function. Our objective was to evaluate the mechanical properties, biochemical composition, transcriptome, and cellular activity of plantarflexor tendons from 4 month old male and female C57BL/6 mice using in vitro biomechanics, mass spectrometry‐based proteomics, genome‐wide expression profiling, and cell culture techniques. While the Achilles tendons of male mice were approximately 6% larger than female mice (p  0.05) of plantaris tendons were observed. Mass spectrometry proteomics analysis revealed no significant difference between sexes in the abundance of major extracellular matrix (ECM) proteins such as collagen types I (p = 0.30) and III (p = 0.68), but female mice had approximately twofold elevations (p < 0.05) in less abundant ECM proteins such as fibronectin, periostin, and tenascin C. The transcriptome of male and female tendons differed by only 1%. In vitro, neither the sex of the serum that fibroblasts were cultured in, nor the sex of the ECM in which they were embedded, had profound effects on the expression of collagen and cell proliferation genes. Our results indicate that while male mice expectedly had larger tendons, male and female tendons have very similar mechanical properties and biochemical composition, with small increases in some ECM proteins and proteoglycans evident in female tendons. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2117–2126, 2017.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138868/1/jor23516-sup-0001-SuppTab-S1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138868/2/jor23516_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138868/3/jor23516-sup-0002-SuppTab-S2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138868/4/jor23516.pd

Insulin‐like growth factor 1 signaling in tenocytes is required for adult tendon growth

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154662/1/fsb2fj201901503r.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154662/2/fsb2fj201901503r-sup-0001.pd

Dermal Sensory Regenerative Peripheral Nerve Interface for Reestablishing Sensory Nerve Feedback in Peripheral Afferents in the Rat

Background: Without meaningful, intuitive sensory feedback, even the most advanced myoelectric devices require significant cognitive demand to control. The dermal sensory regenerative peripheral nerve interface (DS-RPNI) is a biological interface designed to establish high-fidelity sensory feedback from prosthetic limbs. Methods: DS-RPNIs were constructed in rats by securing fascicles of residual sensory peripheral nerves into autologous dermal grafts, with the objectives of confirming regeneration of sensory afferents within DS-RPNIs and establishing the reliability of afferent neural response generation with either mechanical or electrical stimulation. Results: Two months after implantation, DS-RPNIs were healthy and displayed well-vascularized dermis with organized axonal collaterals throughout and no evidence of neuroma. Electrophysiologic signals were recorded proximal from DS-RPNI's sural nerve in response to both mechanical and electrical stimuli and compared with (1) full-thickness skin, (2) deepithelialized skin, and (3) transected sural nerves without DS-RPNI. Mechanical indentation of DS-RPNIs evoked compound sensory nerve action potentials (CSNAPs) that were like those evoked during indentation of full-thickness skin. CSNAP firing rates and waveform amplitudes increased in a graded fashion with increased mechanical indentation. Electrical stimuli delivered to DS-RPNIs reliably elicited CSNAPs at low current thresholds, and CSNAPs gradually increased in amplitude with increasing stimulation current. Conclusions: These findings suggest that afferent nerve fibers successfully reinnervate DS-RPNIs, and that graded stimuli applied to DS-RPNIs produce proximal sensory afferent responses similar to those evoked from normal skin. This confirmation of graded afferent signal transduction through DS-RPNI neural interfaces validate DS-RPNI's potential role of facilitating sensation in human-machine interfacing. Clinical Relevance Statement: The DS-RPNI is a novel biotic-abiotic neural interface that allows for transduction of sensory stimuli into neural signals. It is expected to advance the restoration of natural sensation and development of sensorimotor control in prosthetics.</p

Inhibition of platelet‐derived growth factor signaling prevents muscle fiber growth during skeletal muscle hypertrophy

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136465/1/feb212571-sup-0001-Tables1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136465/2/feb212571_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136465/3/feb212571.pd

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 both 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 plantaris tendons from ambulatory control 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 and monocytes/macrophages (MΦ), heightened expression of inflammation‐related genes, and increased intratendinous concentrations of the pro‐inflammatory eicosanoids thromboxane B2 and prostaglandin E2. By day 7, MΦ became the predominant myeloid cell type in tendon and there were further delayed increases in other COX metabolites including prostaglandins D2, F2α, and I2. Specialized pro‐resolving mediators including protectin D1, resolvin D2 and D6, as well as related pathway markers of D‐resolvins (17‐hydroxy‐docosahexaenoic acid), E‐resolvins (18‐hydroxy‐eicosapentaenoic acid), and lipoxins (15‐hydroxy‐eicosatetraenoic acid) were also increased locally in response to tendon overuse, as were anti‐inflammatory fatty acid epoxides of the CYP pathway (eg, epoxy‐eicosatrienoic acids). Nevertheless, intratendinous prostaglandins remained markedly increased even following 28 days of tendon overuse together with a lingering MΦ 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 specialized pro‐resolving lipid mediators.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/167767/1/fsb221655.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167767/2/fsb221655_am.pd

Inhibition of platelet‐derived growth factor signaling prevents muscle fiber growth during skeletal muscle hypertrophy

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136465/1/feb212571-sup-0001-Tables1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136465/2/feb212571_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136465/3/feb212571.pd

Anterior cruciate ligament tear induces a sustained loss of muscle fiber force production

Introduction: Patients with anterior cruciate ligament (ACL) tears have persistent quadriceps strength deficits that are thought to be due to altered neurophysiological function. Our goal was to determine the changes in muscle fiber contractility independent of the ability of motor neurons to activate fibers. Methods: We obtained quadriceps biopsies of patients undergoing ACL reconstruction, and additional biopsies 1, 2, and 6 months after surgery. Muscles fiber contractility was assessed in vitro, along with whole muscle strength testing. Results: Compared with controls, patients had a 30% reduction in normalized muscle fiber force at the time of surgery. One month later, the force deficit was 41%, and at 6 months the deficit was 23%. Whole muscle strength testing demonstrated similar trends. Discussion: While neurophysiological dysfunction contributes to whole muscle weakness, there is also a reduction in the force generating capacity of individual muscle cells independent of alpha motor neuron activation. Muscle Nerve 58: 145–148, 2018Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145247/1/mus26075.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145247/2/mus26075_am.pd