Obesity and type 2 diabetes mellitus (T2DM) are metabolic diseases at epidemic proportions. The economic burden for these diseases is at an all-time high, and as such, there is an urgent need for advancements in identifying targets for treating these complex disorders. The extracellular matrix (ECM), comprising collagen, fibronectin, laminin, elastin, and proteoglycan, surrounds skeletal muscles and plays a critical role in maintaining tissue homeostasis by providing structural support and facilitating cell-to-cell communication. Disruption of the ECM signaling results in changes to its micro/macroenvironment, thereby modifying tissue homeostasis. Skeletal muscle ECM remodeling has been shown to be associated with insulin resistance, an underlying feature of obesity and T2DM. This narrative review explores the critical components of skeletal muscle ECM and its accumulation and remodeling in metabolic diseases. In addition, we discuss potential treatments to mitigate the effects of ECM remodeling in skeletal muscle. We conclude that targeting ECM remodeling in skeletal muscle represents a promising yet underexplored therapeutic avenue in the management of metabolic disorders.

Skeletal muscle regeneration is a complex process that depends on the interplay between immune responses and muscle stem cell (MuSC) activity. Macrophages play a crucial role in this process, exhibiting distinct polarization states-M1 (pro-inflammatory) and M2 (anti-inflammatory)-that significantly affect tissue repair outcomes. Recent advancements in nanomedicine have positioned gold nanoparticles (Au NPs) as promising tools for modulating macrophage polarization and enhancing muscle regeneration. This review examines the role of Au NPs in influencing macrophage behavior, focusing on their physicochemical properties, biocompatibility, and mechanisms of action. We discuss how Au NPs can promote M2 polarization, facilitating tissue repair through modulation of cytokine production, interaction with cell surface receptors, and activation of intracellular signaling pathways. Additionally, we highlight the benefits of Au NPs on MuSC function, angiogenesis, and extracellular matrix remodeling. Despite the potential of Au NPs in skeletal muscle regeneration, challenges remain in optimizing nanoparticle design, developing targeted delivery systems, and understanding long-term effects. Future directions should focus on personalized medicine approaches and combination therapies to enhance therapeutic efficacy. Ultimately, this review emphasizes the transformative potential of Au NPs in regenerative medicine, offering hope for improved treatments for muscle injuries and diseases.

The cellular viscoelastic modulus in skeletal muscle tissue responds dynamically to chronic stressors, such as age and exercise. Passive tissue mechanics can also be sensitive to acute stimuli, such as mechanical loading and/or activation-induced muscle fatigue. These insights are largely derived from preclinical studies of age and acute muscle activation. Therefore, we sought to understand the relative responsiveness of muscle cellular passive mechanics to chronic (resistance training) and acute (exercise-induced muscle fatigue) stressors in healthy young males and females categorized as 'resistance trained' or 'untrained'. We measured passive mechanics to test the hypothesis that Young's modulus and stress would be greater in fibres from trained versus untrained participants and that both would be reduced following fatigue. We also assessed the translation of these findings to composite tissue in a subset of volunteers where muscle tissue bundles, containing both fibres and extracellular matrix, were analysed in addition to single fibres. We found that resistance-trained individuals demonstrated enhanced passive elastic and viscous modulus compared with non-trained individuals. We also report reductions in passive mechanical measures following fatiguing exercise. Surprisingly, both chronic and acute effectors of passive mechanics were observed in muscle fibres only from males, whereas females showed a more variable response across conditions. Last, we provide preliminary evidence supporting the translation of per-individual cellular differences to the tissue level. Together, these data suggest that males respond more dynamically to acute and chronic stressors of muscle tissue mechanics, potentially linking cellular response and sex-dependent differences in functional outcomes across the lifespan.

Photobiomodulation (PBM) improves collagen distribution and organization in muscles during regeneration, with most data focusing on localized irradiation. Vascular PBM (VPBM) may promote overall muscle recovery and reduce downtime. The aim of the present study was to investigate the effects of VPBM on collagen deposition in muscle tissue after acute injury, comparing preventive (before injury) and therapeutic (after injury) applications. Wistar rats (n = 85) were randomly distributed into groups: Control; Injury; Non-injury + VPBM; Prior-VPBM + Injury; and Injury + Post-injury VPBM. Muscle injury was induced by cryoinjury. VPBM (780 nm, 40 mW, 10 J/cm², 3.2 J) was applied to the caudal artery/vein. Euthanasia occurred on Days 1, 2, 5, and 7 post-injury. Samples were stained with Picrosirius Red to determine areas of collagen and extracellular matrix (ECM). The results revealed increased collagen in the VPBM-treated groups. In the five-day experimental period, the ECM area was significantly lower in the VPBM groups. In conclusion, VPBM modulated collagen deposition and ECM area, depending on the timing of irradiation.

Tendinopathy is a chronic, degenerative disease that has increased prevalence in aged populations, and is characterized by a loss in extracellular matrix (ECM) integrity. Recent work has clearly demonstrated age-related deficits in ECM synthesis with aging, as well as some changes to metabolic activity. Since glucose metabolism is critical to protein synthesis and known to be altered in aging, we sought to investigate if age-related changes in metabolism are linked to changes in ECM remodeling. We used our previously developed flexor tendon explant model to expose young and aged tendon explants to various concentrations of glucose and glutamine supplementation and observe changes in metabolic activity, matrix composition, matrix biosynthesis, and expression of metabolic and ECM genes. We hypothesized that elevated levels of glucose and glutamine would lead to increased ECM remodeling as well as elevated gene expression of their respective pathways in young tendons, with no such effect in aged tendons. Interestingly, we found that glutamine processing is affected by glucose levels with increased expression of key glutamine processing pathways with increased glucose, but this effect was lost with aging. We also observed that ECM remodeling is directly related to both glucose and glutamine processing with altered glycosaminoglycan and collagen synthesis with glucose and glutamine media concentration. Overall, our work reveals that glucose and glutamine are intricately linked for both tenocyte health and ECM homeostasis and that their metabolism could be one of the key drivers of age-related deficiencies in tissue maintenance.

Implantation of a mesh loaded with mesenchymal stem cells (MSCs) is a common approach for the treatment of pelvic organ prolapse (POP). The mesh provides effective support to pelvic floor, enhancing muscle contraction of pelvic organs while reducing inflammation. In this study, a fully degradable mesh is designed for the treatment of POP, utilizing MSCs stimulated by a galvanic battery-powered electric field. The bioelectronic mesh consists of two parts: a galvanic cell film and a porous hydrogel loaded with MSCs. The battery film has a flexible substrate, on which Zinc and Molybdenum film electrodes form a galvanic cell that discharges at up to 1.2 V, stimulating cell proliferation and migration of the MSCs pre-loaded in the hydrogel. The hydrogel provides anchoring and growth sites for the MSCs. The bioelectronic mesh elevates the production of elasticity-related and healing-related factors, enhancing the strength and elasticity of the pelvic tissue and promoting tissue regeneration for POP repair. Compared to traditional stem cell therapy, the local stimulation strategy significantly reduces inflammation in pelvic tissues. In addition, the bioelectronic mesh completely degrades after in vivo application, which avoids risks caused by surgical removal, demonstrating good biocompatibility in the implanted mesh.

Tendinopathy or tendon overuse injury is a major clinical problem for individuals and has a significant socio-economic cost. Its pathophysiology is not yet fully understood and involves multiple factors, including mechanical, cellular and molecular factors. The circadian rhythm has been shown to be a major regulator of extracellular matrix (ECM) homeostasis in several connective tissues, including tendon. Very recently, the human patellar tendon has been established as a peripheral clock tissue that exhibits dampening with chronic tendinopathy, and this has important translational and clinical relevance. This review summarises what is currently known about the role of the tendon circadian clock in collagen and tendon ECM homeostasis and proposes a role for circadian clock disruption in tendinopathy. A better understanding of the mechanisms that regulate tendon clock synchronisation could guide the development of new therapeutic strategies for managing tendon overuse injuries.

Collagens are biofunctional proteins that have been widely used in many fields, including biomedical, cosmetics, and skin care for their value in maintaining the integrity of cellular membranes. Collagens are also commonly consumed in foods and provide a source of protein and amino acids. As part of the safety assessment for this particular recombinant humanized type III (RHTypeIII) collagen produced by Komagataella phaffii SMD1168-2COL3, a series of toxicological tests were conducted. This collagen has ≥ 90% amino acid sequence homology to bovine and porcine collagen. The RHTypeIII collagen showed no evidence of genotoxic potential in a battery of tests. It was not toxic in an acute oral study, with no effects at 10 g/kg BW. The RHTypeIII collagen was not developmentally toxic in Sprague Dawley (SD) rat, and the NOAEL was 4.5 g/kg BW/day. In a 90-day oral gavage study in rats, there were no adverse findings observed; therefore, the high dose level (4.5 g/kg BW/day) was considered the NOAEL. The protein sequence was subjected to homology searches against the AllergenOnline database (sliding 80-amino acid windows and full sequence searches). From the 80-amino acid alignment searches, 23 significant matches were identified (> 35% identity and E value < 1 × 10-7) to allergens of bovine, fish, anisakis, feverfew pollen, ragweed pollen, and wheat origin. Although matches were identified, further assessment of the in silico results combined with a literature review demonstrates that the risk of allergenic cross-reactivity for this collagen is low. These results demonstrate RHTypeIII collagen is not toxic and unlikely to present a risk of allergy when used as a food ingredient.

Postpartum abdominal laxity is a growing concern for women. Noninvasive options like microwave technology and fractional carbon dioxide (CO2) laser show promise, but their combined efficacy and safety require further investigation.

To compare the efficacy and safety of microwaves versus combined microwaves and fractional CO2 laser in the treatment of postpartum abdominal laxity among Filipino patients.

Thirty-two patients with Fitzpatrick skin types III-V and postpartum abdominal laxity received three microwave sessions, with one side randomly assigned an additional fractional carbon dioxide laser session (designated as Side B, while the other as Side A). Global aesthetic improvement scale (GAIS) scores and patient satisfaction (PS) scores were determined at every follow-up. Baseline and completion anthropometric measurements were taken, and adverse effects were recorded.

Significant improvements in GAIS and PS scores were noted for both sides across all sessions (p < 0.001), with side B showing superior scores post-CO2 laser (p < 0.001). A moderate correlation between metabolic equivalent (METs) scores and GAIS scores (p = 0.413, p = 0.019) indicated that higher levels of physical activity were associated with higher GAIS scores. These improvements were attributed to epidermal thickening and dermal collagen and elastin remodeling, the latter seen histologically in a representative patient. Adverse effects were mild and noted only with CO2 laser.

The combined use of the microwave system and fractional CO2 laser is safe and well tolerated and is superior to microwaves alone in the treatment of postpartum abdominal laxity.

Cartilage regeneration requires a specialized biomechanical environment. Macroscopically, cartilage repair requires a protracted, stable mechanical environment, whereas microscopically, it involves dynamic interactions between cells and the extracellular matrix. Therefore, this study aims to design a hydrogel that meets the complex biomechanical requirements for cartilage repair. Dynamic hybrid hydrogels with temporal stability at the macroscale and dynamic properties at the microscale are successfully synthesized. The dynamic hybrid hydrogel simulates the stress relaxation and viscoelasticity of the pericellular matrix, facilitating effective interactions between the extracellular matrix and cells. The in vitro and in vivo experiments demonstrated that the hybrid hydrogel significantly promoted cartilage repair. The dynamic hybrid hydrogel alleviates abnormal actin polymerization, reduces intracellular stress, and increases the volume of individual cells. By modulating the cytoskeleton, the hybrid hydrogel inhibits Notch signal transduction in both the receptor and ligand cells, resulting in an improved cartilage phenotype. This study introduces an effective hybrid hydrogel scaffold that modulates the chondrocyte cytoskeleton and Notch signaling pathways by establishing an appropriate biomechanical environment, thus offering a promising material for cartilage repair.

Lateral epicondylitis (LE) is characterized by enthesopathy and tendon degeneration of the extensor carpi radialis brevis (ECRB) attachment. Although magnetic resonance imaging (MRI) can reveal pathological changes, quantitative evaluation methods remain limited. This study aimed to quantify ECRB tendon degeneration on computed tomography (CT) using Hounsfield unit (HU) values.

We analyzed 24 elbows (12 males, 12 females; mean age: 53.7 years) in the LE group and 25 control elbows (16 males and 9 females; mean age: 56.7 years). All the patients in the study group underwent preoperative CT, MRI, and subsequent ECRB tendon resection. The tendon was divided into proximal, middle, and distal regions. The mean HU values were measured on reconstructed coronal CT images and analyzed in relation to the control group measurements, MRI findings, and histological evaluations.

The mean HU values were significantly lower in the LE group than in the controls in the proximal (49.7 vs. 65.4 HU, P < .0001) and middle regions (58.9 vs. 67.1 HU, P = 0.024) but not in the distal region (66.1 vs. 70.8 HU, P = 0.192). The ECRB tendon showed the greatest histological degeneration proximally, demonstrating a strong negative correlation with HU values (Spearman ρ = -0.612, P < .0001). Proximal region HU values showed a moderate negative correlation with MRI grades (Spearman ρ = -0.517, P = 0.020).

HU values provide a quantitative method for evaluating ECRB tendon degeneration in LE, correlating well with histological and MRI findings. This technique offers an objective measure of tendon pathology that may complement the current diagnostic approaches.

Level III.

Rehabilitation is a crucial component of comprehensive disease management and functional recovery. Despite advancements in surgical techniques for chronic lateral ankle instability (CLAI), there is still a lack of standardized, evidence-based rehabilitation protocols.

After nine clinical questions were proposed by the guidance steering group, an independent search strategy was conducted for all clinical questions, encompassing the PubMed, MEDLINE, Web of Science, EMBASE, and Cochrane databases.

Rehabilitation is crucial to optimize surgical outcomes and patient recovery. An appropriate and well-structured rehabilitation plan can optimize a safe return to sports and daily activities.

Rehabilitation for surgical management of CLAI poses significant challenges, especially in the areas of preoperative preparation, control of postoperative swelling and pain, early-stage rehabilitation, advanced rehabilitation, and return to exercise.

Given the lack of established guidelines for rehabilitation following surgical management of CLAI, this clinical practice guideline presents nine key recommendations aimed at addressing the existing controversies in this area. For CLAI patients undergoing surgery, preoperative rehabilitation should include exercise and education, followed by postoperative focus on pain and swelling management. Early rehabilitation emphasizes nonweight-bearing functional training, with gradual progression to weight-bearing exercises, dynamic balance, and strength training over the first 18 weeks. Regular follow-up visits are essential to monitor recovery and promote functional restoration.

In patients undergoing surgery for CLAI, there is a pressing need for comparative studies to assess the necessity of immobilization and to determine the optimal selection of braces.

Proximal hamstring tendon avulsion injuries are severe and potentially career-threatening for elite athletes. Until now, no data have been published on the non-operative treatment of this injury in elite athletes. Therefore, the objective of this case series was to describe return to performance in elite athletes after non-operative treatment of full-thickness proximal hamstring tendon avulsion injuries as well as provide detailed description of the rehabilitation process and provide a mechanobiological hypothesis on processes leading to successful outcomes.

In this retrospective case series, we included three elite athletes with four MRI-confirmed acute proximal hamstring tendon avulsions of the conjoint tendon and/or the semimembranosus tendon who opted for non-operative treatment following shared decision-making, consisting of an individualised rehabilitation programme. The primary outcome was time to return to performance (in weeks). Secondary outcomes were time to and rate of return to competition, rate of return to performance and re-injury rate.

Four proximal hamstring tendon avulsions in three elite athletes were included. All elite athletes returned to performance within 8-33 weeks, which for three out of four cases was at Olympic (gold medal) level.

This (pilot) case series indicates that non-operative treatment for full-thickness proximal hamstring avulsion injury can result in return to performance in elite athletes. Non-operative treatment may therefore be a viable treatment option in selected (elite) athletes.

The aim of this paper was to undertake a Preferred Reporting Items for Systematic Reviews and Meta-Analysis-accordant meta-analysis comparing exercise-induced muscle damage (EIMD) in older and younger adults.

Google Scholar, PubMed, and SPORTDiscus were searched in June 2023 for the terms "ageing" OR "age" OR "middle-aged" OR "old" OR "older" OR "elderly" OR "masters" OR "veteran" AND "muscle damage" OR "exercise-induced muscle damage" OR "exercise-induced muscle injury" OR "contraction-induced injury" OR "muscle soreness" OR "delayed onset muscle soreness" OR "creatine kinase." From 1,092 originally identified titles, 36 studies were included which had an exercise component comparing a younger against an older group. The outcome variables of EIMD were muscle function, muscle soreness, and creatine kinase. A meta-analysis was conducted on change to EIMD after exercise in older versus younger adults using standardized mean difference (SMD) and an inverse-variance random effects model.

Change after 24 and 72 hr, and peak change, in muscle function was not different between old and young (SMD range = -0.16 to -0.35). Muscle soreness was greater in younger than older adults for all comparisons (SMD range = -0.34 to -0.62). Creatine kinase was greater in younger than older adults at 24 hr (SMD = -0.32), as was peak change (SMD = -0.32). A relationship between sex and peak muscle function change was evident for males (SMD = -0.45), but not females (SMD = -0.44). All other meta-regression was nonsignificant.

Advancing age is not associated with greater symptoms of EIMD. The implication of this study is that the older adults can pursue regular physical activity without concern for experiencing greater EIMD.

Introduction: The paper presents the results concerning the energy (work) and peak power generated by the elevator muscles of the mandible (the masseter, medial pterygoid, and temporalis muscles) during unilateral chewing of selected food products in vitro. Since the act of chewing is a very complex issue in the biomechanics of the masticatory system, the research and analysis of the obtained results were therefore limited to the first cycle. Methods: Determination of the peak energy and power of the muscles required: (1) preparation of food patterns, in the form of the function F = f(Δh) (force (F) vs displacement (Δh)), based on experimental studies and (2) conducting numerical simulations using a 3D kinematic-dynamic model of the human masticatory system. Results and Discussion: Based on the results, the peak energy and power of the muscles were determined based on food patterns. A comparative analysis was also performed to evaluate the energy and peak power generated by the aforementioned muscles during symmetrical incisal biting vs unilateral chewing of the same food products. The results indicate that (1) food height and texture significantly affect muscle energy and (2) the masticatory and medial pterygoid muscles generate more incredible energy and peak power on the working side than on the non working side, while the opposite was observed for the temporalis muscle and (3) comparative analysis showed that food position on the dental arch has a more significant effect on muscle peak power for foods with high texture heterogeneity than for foods with low texture heterogeneity.

Tendinopathy is a prevalent musculoskeletal condition that affects both aging populations and individuals involved in repetitive, high-intensity activities, such as athletes. Current treatment options primarily address symptom management or involve surgery, which carries a significant risk of complications and re-injury. This highlights the need for regenerative medicine approaches that combine stem cells, biomaterials, and growth factors. However, achieving effective tenogenic differentiation remains challenging due to the absence of standardized differentiation protocols. Consequently, a review of existing research has been conducted to identify optimal biomaterial properties and growth factor protocols. Findings suggest that the ideal biomaterial for tenogenic differentiation should feature a 3D structure to preserve tenogenic expression, incorporate a combination of aligned micro- and nanofibers to promote differentiation, and require further investigation into optimal stiffness. Additionally, growth factor protocols should include an induction phase to initiate tenogenic lineage commitment, followed by a maintenance phase to support matrix production and maturation.

The extracellular matrix (ECM) is a complicated milieu consisting of structural and functional molecules secreted by the resident cells that provides an optimal microenvironmental niche for enhanced cell adhesion, growth, differentiation, and tissue formation and maturation. For decades, ECM bio-scaffolds prepared from decellularized tissues have been used to promote skeletal muscle regeneration; however, it was recently discovered that these decellularized ECM (dECM) materials can be further processed into hydrogels, thus expanding the potential applications of dECM materials in skeletal muscle regenerative engineerisng (SMRE). This review article highlights the recent advances in dECM-derived hydrogels toward skeletal muscle regeneration and repair.

We screened articles in PubMed and bibliographic search using a combination of keywords. Relevant and high-cited articles were chosen for inclusion in this narrative review.

Here, we discuss the skeletal muscle ECM's structure, function, and biochemical composition with emphasis on the role of the ECM during skeletal muscle embryogenesis, growth, development, and repair. Furthermore, we review various hydrogels used to promote skeletal muscle regeneration. We also review the current applications of dECM-derived hydrogels toward SMRE. Finally, we discuss the clinical translation potential of dECM-derived hydrogels for skeletal muscle regeneration and repair and their potential clinical considerations in the future.

Although much progress has been made in the field of dECM-derived hydrogels toward SMRE, it is still in its nascent stage. We believe improving and standardizing the methods of decellularization, lowering the immunogenicity of dECMs, and carrying out in vivo investigations in large animal models would advance their future clinical applications.

Researchers have discovered an effective way to turn tissue materials into jelly-like substances known as extracellular matrix (ECM)-derived hydrogels. These ECM-derived hydrogels can help muscles heal better after serious injuries. They can be injected into gaps or used to guide muscle growth in the lab or body. This review article explains how these ECM-derived hydrogels are made and how they can be used to improve muscle healing. It also discusses their possible use in clinics and what needs to be considered before using them for medical treatments.

Following anterior cruciate ligament (ACL) injury, quadriceps muscle atrophy persists despite rehabilitation, leading to loss of lower limb strength, osteoarthritis, poor knee joint health and reduced quality of life. However, the molecular mechanisms responsible for these deficits in hypertrophic adaptations within the quadriceps muscle following ACL injury and reconstruction are poorly understood. While resistance exercise training stimulates skeletal muscle hypertrophy, attenuation of these hypertrophic pathways can hinder rehabilitation following ACL injury and reconstruction, and ultimately lead to skeletal muscle atrophy that persists beyond ACL reconstruction, similar to disuse atrophy. Numerous studies have documented beneficial roles of nutritional support, including nutritional supplementation, in maintaining and/or increasing muscle mass. There are three main mechanisms by which nutritional supplementation may attenuate muscle atrophy and promote hypertrophy: (1) by directly affecting muscle protein synthetic machinery; (2) indirectly increasing an individual's ability to work harder; and/or (3) directly affecting satellite cell proliferation and differentiation. We propose that nutritional support may enhance rehabilitative responses to exercise training and positively impact molecular machinery underlying muscle hypertrophy. As one of the fastest growing knee injuries worldwide, a better understanding of the potential mechanisms involved in quadriceps muscle deficits following ACL injury and reconstruction, and potential benefits of nutritional support, are required to help restore quadriceps muscle mass and/or strength. This review discusses our current understanding of the molecular mechanisms involved in muscle hypertrophy and disuse atrophy, and how nutritional supplements may leverage these pathways to maximise recovery from ACL injury and reconstruction.

The hierarchical structure of tendon dictates its ability to effectively transmit loads from muscle to bone. Tendon- and site-specific differences in mechanical loading result in the establishment and remodeling of structure, as well as associated changes in composition throughout development and healing. Previous work has demonstrated region-specific differences in the response of collagen fibrils to mechanical loading within the insertion region and midsubstance regions of mouse supraspinatus tendons using atomic force microscopy. However, multiscale structure, function, and gene expression differences between the insertion and midsubstance of the supraspinatus tendon have not yet been linked together in a comprehensive study. Therefore, the purpose of this study was to elucidate site-specific hierarchical structure, function, and gene expression differences in mouse supraspinatus tendons. Supraspinatus tendons from day 150 wild-type C57BL/6 mice were harvested for regional mechanics, histology, transmission electron microscopy (TEM), and quantitative polymerase chain reaction (qPCR). Mechanical testing revealed that the midsubstance region demonstrated a greater modulus and increased collagen fiber realignment compared to the insertion region. Histological scoring demonstrated greater cellularity and more rounded cells in the insertion region. TEM analysis showed differences in collagen fibril diameter distributions between the two regions, with a shift towards smaller diameters observed at the insertion region. Gene expression analysis identified several genes that were differentially expressed between regions, with principal component analysis revealing distinct clustering based on region. These findings provide insight into the regional heterogeneity of the supraspinatus tendon and underscore the importance of considering these differences in the context of tendon injury and repair, contributing to a better understanding of tendon structure-function and guiding future studies aimed at elucidating the mechanisms underlying tendon pathology.

Musculoskeletal discomfort is prevalent in primary care, with conditions such as osteoarthritis and osteoporosis being significant contributors. Collagen, particularly type I, is a major structural protein found in connective tissues. The supplementation of type I hydrolyzed collagen has been investigated for its potential benefits in musculoskeletal health.

This systematic review aims to evaluate the current literature on the effects of type I hydrolyzed collagen supplementation on bones, muscles, and joints.

A systematic search was conducted in August 2024 using four electronic databases - PubMed, Scopus, EMBASE, and CINAHL. The inclusion criteria were randomized controlled trials (RCTs) and systematic reviews evaluating oral supplementation with type I hydrolyzed collagen. Exclusion criteria were pre-clinical studies, experimental studies, studies not focusing on type I hydrolyzed collagen, studies with beauty-related endpoints, studies that combined collagen with other ingredients, and unblinded, nonrandomized, and uncontrolled trials.

Out of 4,246 articles screened, 36 RCTs met the inclusion criteria. The study protocols varied in population, health conditions, and study duration. Studies focused on bone health faced limitations that prevent definitive conclusions about the effects of collagen supplementation. In contrast, studies on joint health reported beneficial outcomes, such as pain reduction, improvements in clinical parameters, increased physical mobility, and enhanced ankle function. The muscle health studies were inconsistent, with positive effects predominantly observed when supplementation was associated with physical exercise.

Collagen supplementation demonstrates promising results. However, heterogeneity among studies limits the generalizability of findings. Future research should prioritize standardized protocols and consistent outcome measures.

Background: The extracellular matrix (ECM) plays a critical role in the proper regeneration of skeletal muscle. ECM remodeling has been reported in the skeletal muscle of chronic obstructive pulmonary disease (COPD), while the mechanisms remain poorly understood. Methods: In this study, we examined the dynamic interplay between ECM components and ECM enzymes in COPD skeletal muscle and cigarette smoke (CS) extract-treated C2C12 cells. C2C12 cells were further used to evaluate the role of a disintegrin and metalloproteinase with thrombospondin motif 4 (ADAMTS4) in ECM remodeling and myogenesis. Results: Chronic CS exposure induced the development of COPD and comorbid sarcopenia in C57BL/6J mice. Muscle fibrosis was observed in the gastrocnemius muscle of CS-exposed mice, accompanied by an upregulation of protein expression but a downregulation of mRNA levels of fibronectin and versican. We found that the discrepancy of mRNA and protein expression was attributed to the aberrant secretion of some ECM enzymes belonging to matrix metalloproteinases and ADAMTS proteases, especially ADAMTS4. CS exposure reduced ADAMTS4 expression in gastrocnemius muscles and C2C12 cells, and Adamts4 knockdown induced fibronectin and versican accumulation and impeded myogenic process. Conclusions: Considering that recent studies have indicated an impaired skeletal muscle regeneration in COPD, we suggested that the restrained production of ADAMTS4 in response to CS could be involved in the damaged muscle regeneration through regulating skeletal muscle ECM in COPD. Targeting ECM enzymes may benefit the rehabilitation of COPD-related sarcopenia.

Tendinopathy is a condition characterized by persistent tendon pain, structural damage, and compromised functionality. Presently, the treatment for tendinopathy remains a formidable challenge, partly because of its unclear pathogenesis. Tendon stem/progenitor cells (TSPCs) are essential for tendon homeostasis, regeneration, remodeling, and repair. An innovative theory has been previously proposed, with insufficient evidence, that the erroneous differentiation of TSPCs may constitute one of the fundamental mechanisms underpinning tendinopathy. Over the past few years, there has been accumulating evidence for plausibility of this theory. In this review, we delve into alterations in the differentiation potential of TSPCs and the underlying mechanisms in the context of injury-induced tendinopathy, diabetic tendinopathy, and age-related tendinopathy to provide updated evidence on the erroneous differentiation theory. Despite certain limitations inherent in the existing body of evidence, the erroneous differentiation theory emerges as a promising and highly pertinent avenue for understanding tendinopathy. In the future, advanced methodologies will be harnessed to further deepen comprehension of this theory, paving the way for prospective developments in clinical therapies targeting TSPCs for the management of tendinopathy.

Tendon injuries and disorders associated with mechanical tendon overuse are common musculoskeletal problems. Even though tendons play a central role in human movement, the intrinsic healing process of tendon is very slow. So far, it is known that tendon cell activity is supported by several interstitial cells within the tendon. However, the interplay between the tendon and the adjacent muscle for tendon regeneration and development processes has not been fully investigated. Here, we tested whether factors released from muscle derived myogenic cells (myoblasts) enhance tenogenic progressions of human tendon derived cells (tendon fibroblasts) using two-dimensional (2D) culture model and a three-dimensional (3D)-engineered tendon construct culture model, which mimics tendon regeneration and development. The conditioned media from myoblasts and unconditioned media as control were applied to tendon fibroblasts. In 2D, immunofluorescence analysis revealed increased collagen type I expressing area and increased migration potential when conditioned media from myoblasts were applied. In the 3D-engineered human tendon construct model, wet weight, diameter, and cross-sectional area of the tendon constructs were increased in response to the application of conditioned media from myoblasts, whereas the collagen density was lower and mechanical function was reduced both at the functional level (maximum stiffness) and the material level (maximum stress and modulus). These results indicate that myoblast-derived factors extend collagen expressing area and enhance migration of tendon fibroblasts, while factors involved in the robustness of extra-cellular matrix deposition of tissue-engineered tendon constructs are lacking. Our findings suggest that adjacent muscle affects the signaling interplay in tendons.

In individuals with chronic post-stroke hemiparesis, slow walking speed is a significant concern related to inadequate propulsion of the paretic limb. However, an overlooked factor is this population's altered morphology of the Achilles tendon, which may compromise the propulsive forces by the paretic limb. This study aimed to explore changes in Achilles tendon morphology, including gross thickness and intra-tendinous collagen fiber bundle organization, following stroke-induced brain lesions.

Fifteen individuals with chronic post-stroke hemiparesis (at least 6 months post-stroke) and 19 neurologically intact controls participated. Ultrasound imaging was used to evaluate Achilles tendon thickness and collagen organization in the paretic and non-paretic limbs of post-stroke participants, as well as in the right limb (control limb) of the neurologically intact control group.

Compared to control individuals, the paretic limb in individuals post-stroke showed increased tendon thickness at the Achilles tendon insertion and 2 cm above it. The collagen fiber bundle at the Achilles tendon insertion of the paretic limb showed reduced organization compared to that in the control limb. Individuals post-stroke also exhibited slower walking speed, and increased plantarflexor muscle tone in the paretic limb compared to controls. In conclusion, individuals with chronic post-stroke hemiparesis demonstrated tendon thickening and collagen disorganization in the paretic limb, particularly at the insertion site of the Achilles tendon, likely due to an abnormal loading environment influenced by increased plantarflexor muscle tone, muscle co-activation, and muscle disuse and atrophy. These changes may increase tendon compliance, impair force transmission and propulsion, and contribute to slower walking speed. Addressing Achilles tendon integrity should be incorporated as a component of strategies to improve neuromuscular control in this population.

Optimal loading involves the prescription of an exercise stimulus that promotes positive tissue adaptation, restoring function in patients undergoing rehabilitation and improving performance in healthy athletes. Implicit in optimal loading is the need to monitor the response to load, but what constitutes a normal response to loading? And does it differ among tissues (e.g., muscle, tendon, bone, cartilage) and systems? In this paper, we discuss the "normal" tissue response to loading schema and demonstrate the complex interaction among training intensity, volume, and frequency, as well as the impact of these training variables on the recovery of specific tissues and systems. Although the response to training stress follows a predictable time course, the recovery of individual tissues to training load (defined herein as the readiness to receive a similar training stimulus without deleterious local and/or systemic effects) varies markedly, with as little as 30 min (e.g., cartilage reformation after walking and running) or 72 h or longer (e.g., eccentric exercise-induced muscle damage) required between loading sessions of similar magnitude. Hyperhydrated and reactive tendons that have undergone high stretch-shorten cycle activity benefit from a 48-h refractory period before receiving a similar training dose. In contrast, bone cells desensitize quickly to repetitive loading, with almost all mechanosensitivity lost after as few as 20 loading cycles. To optimize loading, an additional dose (≤ 60 loading cycles) of bone-centric exercise (e.g., plyometrics) can be performed following a 4-8 h refractory period. Low-stress (i.e., predominantly aerobic) activity can be repeated following a short (≤ 24 h) refractory period, while greater recovery is needed (≥ 72 h) between repeated doses of high stress (i.e., predominantly anaerobic) activity. The response of specific tissues and systems to training load is complex; at any time, it is possible that practitioners may be optimally loading one tissue or system while suboptimally loading another. The consideration of recovery timeframes of different tissues and systems allows practitioners to determine the "normal" response to load. Importantly, we encourage practitioners to interpret training within an athlete monitoring framework that considers external and internal load, athlete-reported responses, and objective markers, to contextualize load-response data.

This systematic review and meta-analysis aimed to identify the association between genetic polymorphisms and tendon and ligament injuries in adolescent and adult athletes of multiple competition sports. The PubMed, Web of Science, EBSCO, Cochrane Library, and MEDLINE databases were searched until July 7, 2023. Eligible articles included genetic studies on tendon and ligament injuries and comparisons between injured and non-injured athletes. This review included 31 articles, comprising 1,687 injury cases and 2,227 controls, from a meta-analysis of 12 articles. We identified 144 candidate gene polymorphisms (only single nucleotide polymorphisms were identified). The meta-analyses included vascular endothelial growth factor A (VEGFA) rs699947, collagen type I alpha 1 rs1800012, collagen type V alpha 1 rs12722, and matrix metalloproteinase 3 rs679620. The VEGFA rs699947 polymorphism showed a lower risk of injuries in athletes with the C allele ([C vs. A]: OR=0.80, 95% CI: 0.65-0.98, I 2 =3.82%, p=0.03). The risk of these injuries were not affected by other polymorphisms. In conclusion, the VEGFA rs699947 polymorphism is associated with the risk of tendon and ligament injuries in athletes. This study provides insights into genetic variations that contribute to our understanding of the risk factors for such injuries in athletes.

Zebrafish (Danio rerio) have emerged as a valuable model organism for investigating musculoskeletal development and the pathophysiology of associated diseases. Key genes and biological processes in zebrafish that closely mirror those in humans, rapid development, and transparent embryos make zebrafish ideal for the in vivo studies of bone and muscle formation, as well as the molecular mechanisms underlying musculoskeletal disorders. This review focuses on the utility of zebrafish in modeling various musculoskeletal conditions, with an emphasis on bone diseases such as osteoporosis and osteogenesis imperfecta, as well as muscle disorders like Duchenne muscular dystrophy. These models have provided significant insights into the molecular pathways involved in these diseases, helping to identify the key genetic and biochemical factors that contribute to their progression. These findings have also advanced our understanding of disease mechanisms and facilitated the development of potential therapeutic strategies for musculoskeletal disorders.

Although current treatments for Duchenne Muscular Dystrophy (DMD) have proven to be effective in delaying myopathy, there remains a strong need to identify novel targets to develop additional therapies. Mitochondrial dysfunction is an early pathological feature of DMD. A fine balance of mitochondrial dynamics (fission and fusion) is crucial to maintain mitochondrial function and skeletal muscle health. Excessive activation of Dynamin-Related Protein 1 (Drp1)-mediated mitochondrial fission was reported in animal models of DMD. However, whether Drp1-mediated mitochondrial fission is a viable target for treating myopathy in DMD remains unknown. Here, we treated a D2-mdx model of DMD (9-10 weeks old) with Mdivi-1, a selective Drp1 inhibitor, every other day (i.p. injection) for 5 weeks. We demonstrated that Mdivi-1 effectively improved skeletal muscle strength and reduced serum creatine kinase concentration. Mdivi-1 treatment also effectively inhibited mitochondrial fission regulatory protein markers, Drp1(Ser616) phosphorylation and Fis1 in skeletal muscles from D2-mdx mice, which resulted in reduced content of damaged and fragmented mitochondria. Furthermore, Mdivi-1 treatment attenuated lipid peroxidation product, 4-HNE, in skeletal muscle from D2-mdx mice, which was inversely correlated with muscle grip strength. Finally, we revealed that Mdivi-1 treatment downregulated Alpha 1 Type I Collagen (Col1a1) protein expression, a marker of fibrosis, and Interleukin-6 (IL-6) mRNA expression, a marker of inflammation. In summary, these results demonstrate that inhibition of Drp1-mediated mitochondrial fission by Mdivi-1 is effective in improving muscle strength and alleviating muscle damage in D2-mdx mice. These improvements are associated with improved skeletal muscle mitochondrial integrity, leading to attenuated lipid peroxidation.

The aponeurosis is a large fibrous connective tissue structure within and surrounding skeletal muscle and is a critical component of the muscle-tendon unit (MTU). Due to the lack of consensus on terminology and the heterogeneous nature of the aponeurosis between MTUs, there are several questions that remain unanswered. For example, the aponeurosis is often conflated with the free tendon rather than being considered an independent structure. This has subsequent implications when interpreting data regarding the structure, function, and adaptation of the aponeuroses from these studies. In recent years, a body of work has emerged to suggest that acute injury to the myo-aponeurotic complex may have an impact on return-to-sport timeframes and reinjury rates. Therefore, the purpose of this review is to provide a more detailed understanding of the morphology and mechanical behaviour common to all aponeuroses, as well as the unique characteristics of specific lower-limb aponeuroses that are commonly injured. This review provides the practitioner with a current understanding of the mechanical, material, and adaptive properties of lower limb aponeuroses and suggests directions for future research related to the myo-aponeurotic complex.

Anterior Cruciate Ligament (ACL) injuries rank among the most prevalent and severe types of injuries, significantly impacting both athletes and non-athletes alike. These injuries not only result in immediate physical impairment, such as intense pain, substantial swelling, and a marked loss of mobility, but also carry long-term health consequences that can alter a person's quality of life. Chronic pain, persistent instability, and an increased risk of developing osteoarthritis are among the lasting effects that can follow an ACL injury. An in-depth understanding of the biophysics behind ACL injuries is paramount for devising effective prevention and treatment protocols. Biophysics, which combines principles from physics with biological systems, provides crucial insights into the mechanical and structural integrity of the ACL and its susceptibility to injury under various conditions. This systematic review aims to collate and synthesize the current knowledge surrounding the biophysical mechanisms that underlie ACL injuries.

The Achilles tendon (AT) may become smaller in volume following acute bouts of heavy and sustained loading likely because of transient fluid exudation to the periphery and this could augment cellular mechanotransduction and tendon adaptation. Given the structure of the AT is distinct across its length, regional changes in the free AT volume may occur in response to loading. This study aimed to investigate whether the change in tendon volume in response to repeated submaximal loading is distinct across the free AT length.

Sixteen ATs of healthy males and females (age 24.4 ± 9.4 years, body mass 70.9 ± 16.1 kg, height 1.7 ± 0.1 m) were scanned at rest using freehand 3D ultrasound. Scanning was done before and immediately after submaximal (75 %) voluntary isometric plantarflexion contractions (8 s) involving four sets of ten repetitions. Regional volumetric changes were assessed across the free AT length by dividing the tendon into distal, mid, and proximal regions.

Significant reduction in the free AT volume occurred across all tendon regions in response to the intervention, however, the mid- region exhibited the greatest reduction in volume compared to the proximal region (P = 0.025).

The fact that volume reduction was greatest in the mid-region compared to the proximal region of the free AT may suggest greater tendon adaptation, via mechanotransduction pathways, in the mid-region and this may be important for tendon health and injury prevention.

In the past two decades, interest in the fascial system has exponentially increased, particularly manual treatment and stretching exercises. The fascia's fundamental role remains the transmission of tensions, although this function can be impaired due to excessive or reduced stiffness. This second part of the work outlines the basic principles concerning the importance of appropriate and balanced fascial stiffness for correct postural and functional maintenance of the human body. Additionally, the limited studies available in the literature are reviewed, with a focus on therapeutic exercises aimed at increasing fascial system stiffness. The article addresses how fascia develops the ability to contract to maintain a physiological tension referred to as human resting myofascial tone. Additionally, it discusses the most recognized tools for assessing fascial tension: myotonometry and shear wave elastography. The final section is dedicated to presenting the current literature on the relationship between physical exercise and fascial stiffness.

Although the female athlete triad (Triad) has been associated with increased risk of bone-stress injuries (BSIs), limited research among collegiate athletes has addressed the associations between the Triad and non-BSI injuries.

To elucidate the relationship between Triad and both BSI and non-BSI in female athletes.

Retrospective cohort study.

Primary and tertiary care student athlete clinic.

National Collegiate Athletic Association Division I female athletes at a single institution.

Participants completed a pre-participation questionnaire and dual-energy x-ray absorptiometry, which was used to generate a Triad cumulative risk assessment score (Triad score). The number of overuse musculoskeletal injuries that occurred while the athletes were still competing collegiately were identified through chart review.

BSI and non-BSI were treated as count variables. The association between BSI, non-BSI, and Triad score was measured using Poisson regression to calculate rate ratios.

Of 239 athletes, 43% of athletes (n = 103) sustained at least one injury. Of those, 40% (n = 95) sustained at least one non-BSI and 10% (n = 24) sustained at least one BSI over an average follow-up 2.5 years. After accounting for sport type (non-lean, runner, other endurance sport, or other lean advantage sport) and baseline age, we found that every additional Triad score risk point was associated with a significant 17% increase in the rate of BSI (rate ratio [RR] 1.17, 95% confidence interval [CI] 1.03-1.33; p = .016). However, Triad score was unrelated to non-BSI (1.00, 95% CI 0.91-1.11; p = .99). Compared with athletes in non-lean sports (n = 108), athletes in other lean advantage sports (n = 30) had an increased rate of non-BSI (RR: 2.09, p = .004) whereas distance runners (n = 46) had increased rates of BSI (RR: 7.65, p < .001) and non-BSI (RR: 2.25, p < .001).

Higher Triad score is associated with an increased risk of BSI but not non-BSI in collegiate athletes.

Protein supplementation increases postexercise muscle protein synthesis rates and, as such, supports exercise-induced muscle conditioning. Collagen protein has been suggested as the preferred protein source to stimulate muscle connective protein synthesis rates during recovery from exercise. Here we assessed the effects of hydrolyzed collagen peptide supplementation on both myofibrillar as well as muscle connective protein synthesis rates during 1 wk of strenuous resistance exercise training.

In a randomized, double-blind, parallel design, 25 young men (24 ± 3 yr, 76.9 ± 6.4 kg) were selected to perform 1 wk of intense resistance-type exercise training. Subjects were randomly assigned into two groups receiving either 15 g hydrolyzed collagen peptides (COL) or a noncaloric placebo (PLA) twice daily during the intervention. Subjects were administered deuterated water ( 2 H 2 O) daily, with blood and skeletal muscle tissue samples being collected before and after the intervention to determine daily myofibrillar and muscle connective protein synthesis rates.

Post-absorptive plasma glycine, proline, and hydroxyproline concentrations increased following collagen peptide supplementation ( P < 0.05) and showed higher levels when compared with the placebo group ( P < 0.05). Daily muscle connective protein synthesis rates during the intervention period exceeded myofibrillar protein synthesis rates (1.99 ± 0.38 vs 1.34 ± 0.23%·d -1 , respectively; P < 0.001). Collagen peptide supplementation did not result in higher myofibrillar or muscle connective protein synthesis rates (1.34 ± 0.19 and 1.97 ± 0.47%·d -1 , respectively) when compared with the placebo group (1.34 ± 0.27 and 2.00 ± 0.27%·d -1 , respectively; P > 0.05).

Collagen peptide supplementation (2 × 15 g daily) does not increase myofibrillar or muscle connective protein synthesis rates during 1 wk of intense resistance exercise training in young, recreational athletes.

Skeletal muscle tissue function is governed by the mechanical properties and organization of its components, including myofibers, extracellular matrix, and adipose tissue, which can be modified by the onset and progression of many disorders. This study used a novel combination of quantitative micro-elastography and clearing-enhanced three-dimensional (3D) microscopy to assess 3D micro-scale elasticity and micro-architecture of muscles from two muscular dystrophies: dysferlinopathy and Duchenne muscular dystrophy, using male BLA/J and mdx mice, respectively, and their wild-type (WT) controls. We examined three muscles with varying proportions of slow- and fast-twitch myofibers: the soleus (predominantly slow), extensor digitorum longus (EDL; fast), and quadriceps (mixed), from BLA/J and WTBLA/J mice aged 3, 10, and 24 months, and mdx and WTmdx mice aged 10 months. Both dysferlin deficiency and age reduced the elasticity and variability of elasticity of the soleus and quadriceps, but not EDL. Overall, the BLA/J soleus was 20% softer than WT and less mechanically heterogeneous (-14% in standard deviation of elasticity). The BLA/J quadriceps at 24 months was 72% softer than WT and less mechanically heterogeneous (-59% in standard deviation), with substantial adipose tissue accumulation. While mdx muscles did not differ quantitatively from WT, regional heterogeneity was evident in micro-scale elasticity and micro-architecture of quadriceps (e.g., 11.2 kPa in a region with marked pathology vs 3.8 kPa in a less affected area). These results demonstrate differing biomechanical changes in hind-limb muscles of two distinct muscular dystrophies, emphasizing the potential for this novel multimodal technique to identify important differences between various myopathies.

The transcriptional heterogeneity at a single-nucleus level in human Becker muscular dystrophy (BMD) dystrophic muscle has not been explored. Here, we aimed to understand the transcriptional heterogeneity associated with myonuclei, as well as other mononucleated cell types that underly BMD pathogenesis by performing single-nucleus RNA sequencing.

We profiled single-nucleus transcriptional profiles of skeletal muscle samples from 7 BMD patients and 3 normal controls.

A total of 17,216 nuclei (12,879 from BMD patients and 4,337 from controls) were classified into 13 known cell types, including 9 myogenic lineages and 4 non-myogenic lineages, and 1 unclassified nuclear type according to their cell identities. Among them, type IIx myonuclei were the first to degenerate in response to dystrophin reduction. Differential expression analysis revealed that the fibro-adipogenic progenitors (FAPs) population had the largest transcriptional changes among all cell types. Sub-clustering analysis identified a significantly compositional increase in the activated FAPs (aFAPs) subpopulation in BMD muscles. Pseudotime analysis, regulon inference, and deconvolution analysis of bulk RNA-sequencing data derived from 29 BMD patients revealed that the aFAPs subpopulation, a distinctive and previously unrecognized mononuclear subtype, was profibrogenic and expanded in BMD patients. Muscle quantitative real-time polymerase chain reaction and immunofluorescence analysis confirmed that the mRNA and protein levels of the aFAPs markers including LUM, DCN, and COL1A1 in BMD patients were significantly higher than those in controls, respectively.

Our results provide insights into the transcriptional diversity of human BMD muscle at a single-nucleus resolution and new potential targets for anti-fibrosis therapies in BMD. ANN NEUROL 2024;96:1070-1085.

Resistance exercise upregulates and downregulates the expression of a wide range of genes in skeletal muscle. However, detailed analysis of mRNA dynamics such as response rates and temporal patterns of the transcriptome after resistance exercise has not been performed. We aimed to clarify the dynamics of time-series transcriptomics after resistance exercise. We used electrical stimulation-induced muscle contraction as a resistance exercise model (5 sets × 10 times of 3 s of 100-Hz electrical stimulation) on the tibialis anterior muscle of rats and measured the transcriptome in the muscle before and at 0, 1, 3, 6, and 12 h after muscle contractions by RNA sequencing. We also examined the relationship between the parameters of mRNA dynamics and the increase in protein expression at 12 h after muscle contractions. We found that the function of the upregulated genes differed after muscle contractions depending on their response rate. Genes related to muscle differentiation and response to mechanical stimulus were enriched in the sustainedly upregulated genes. Furthermore, there was a positive correlation between the magnitude of upregulated mRNA expression and the corresponding protein expression level at 12 h after muscle contractions. Although it has been theoretically suggested, this study experimentally demonstrated that the magnitude of the mRNA response after electrical stimulation-induced resistance exercise contributes to skeletal muscle adaptation via increases in protein expression. These findings suggest that mRNA expression dynamics such as response rate, a sustained upregulated expression pattern, and the magnitude of the response contribute to mechanisms underlying adaptation to resistance exercise.

Limited research has focused on the correlation between an external compression and the regeneration of ruptured Achilles tendons. The aim of this study was to evaluate the influence of a constricted paratenon with external compression on the regeneration process of separated rabbit common calcanean tendon stumps.

A transection, establishing a 4 mm gap, was created in the right common calcanean tendon of 24 young adult male New Zealand white rabbits. The animals were assigned to two groups: In the control group, only received cast immobilization. In the constricted paratenon (CP) group, the rabbits had a local 3-dimensional printed clasp applied to mimic external compression and same cast immobilization as the control group. Morphologic, histologic and immunohistochemistry examinations were performed at 2 and 4 weeks postoperative.

Separated tendon stumps were connected by novel granulated tendon fibrils in the control group. However, the regenerated tendon fibrils appeared insufficient in the CP group, the tendon length and the adhesion grade of the CP group was significantly larger than that of the control group at 4 weeks (P < 0.05, P = 0.030). Disorganized collagen and round-shaped fibroblasts were demonstrated in the CP group. A prolonged expression of proliferating cell nuclear antigen (PCNA) and lower intensity in clusters of differentiation 146 (CD146) were also shown in the CP group. A prolonged existence of the vascular endothelial growth factor (VEGF) and lesser intensity of the transforming growth factor-beta 1 (TGF-β1) were confirmed within this group. Furthermore, the CP group's expression had less collagen I than that of the control group at 4 weeks.

Sufficient regeneration can be obtained, even though there is an obvious gap between severed rabbit common calcanean tendon stumps. However, constricted paratenons with external compression can negatively influence the intrinsic regeneration process of the tendon fibrils and promotes the disorganization of regenerated collagen.

The actin cytoskeleton is a potent regulator of tenocyte homeostasis. However, the mechanisms by which actin regulates tendon homeostasis are not entirely known. This study examined the regulation of tenocyte molecule expression by actin polymerization via the globular (G-) actin-binding transcription factor, myocardin-related transcription factor-a (MRTF). We determined that decreasing the proportion of G-actin in tenocytes by treatment with TGFβ1 increases nuclear MRTF. These alterations in actin polymerization and MRTF localization coincided with favorable alterations to tenocyte gene expression. In contrast, latrunculin A increases the proportion of G-actin in tenocytes and reduces nuclear MRTF, causing cells to acquire a tendinosis-like phenotype. To parse out the effects of F-actin depolymerization from regulation by MRTF, we treated tenocytes with cytochalasin D. Exposure of cells to cytochalasin D increases the proportion of G-actin in tenocytes. However, as compared to latrunculin A, cytochalasin D has a differential effect on MRTF localization by increasing nuclear MRTF. This led to an opposing effect on the regulation of a subset of genes. The differential regulation of genes by latrunculin A and cytochalasin D suggests that actin signals through MRTF to regulate a specific subset of genes. By targeting the deactivation of MRTF through the inhibitor CCG1423, we verify that MRTF regulates Type I Collagen, Tenascin C, Scleraxis, and α-smooth muscle actin in tenocytes. Actin polymerization status is a potent regulator of tenocyte homeostasis through the modulation of several downstream pathways, including MRTF. Understanding the regulation of tenocyte homeostasis by actin may lead to new therapeutic interventions against tendinopathies, such as tendinosis.

Morphologic Achilles tendon properties obtained via diagnostic ultrasound imaging are valuable in understanding Achilles tendon health and injury. Currently, limited information exists regarding Achilles tendon morphological properties amongst active aging adults based upon Victorian Institute of Sport Assessment (VISA-A) scores. Achilles tendon morphologic properties defined by VISA-A score groupings allow clinicians and researchers to compare data values amongst current patients. Purpose: Comparison of physically active aging adults Achilles tendon morphological properties with various VISA-A scores or a previous Achilles tendon rupture. A convenience sample of 121 participants (71 females, 50 males) at least moderately active and 50 years old, were recruited. Participants completed a VISA-A survey, and assigned groups by scores (Group 1: 90-100, Group 2: 70-89, Group 3: 45-69, Group 4: Previous Achilles tendon tear). Achilles tendon ultrasound imaging occurred at the malleolar line (The apex of the medial and lateral malleolus). Following imaging Achilles tendon cross-sectional area (CSA), thickness, and elastography were measured and analyzed. Participants with a previous Achilles tendon rupture displayed significantly larger tendon CSA and thickness compared with other groups (p<0.05). Individuals with VISA-A scores from 45-69 displayed significantly larger tendon CSA and thickness than participants with scores greater than 90 (p<0.03). No significant differences were noted for elastography between groups (p>0.05). Achilles tendon morphological differences exist based upon pain level in physically active aging adults. Diagnostic ultrasound may be used during assessment and rehabilitation of injured tendon tissue to inform about current tendon tissue properties.

Resistance exercise (RE) increases collagen synthesis in young and older men, whereas hydrolyzed collagen (HC) ingestion improves this response to RE in a dose-response manner in young men. However, the collagen synthesis response to RE with and without HC in middle-aged men is unknown. Eight resistance-trained men (age: 49 ± 8 yr; height: 1.78 ± 0.02 m; mass: 90 ± 4 kg) took part in this double-blind, crossover design study and undertook 4 × 10 repetitions of lower-limb RE at maximum load, after consuming 0 g, 15 g, or 30 g vitamin C-enriched HC. We analyzed venous blood samples for N-terminal propeptide of type 1 pro-collagen (PINP), β-isomerized C-terminal telopeptide of type 1 collagen (β-CTx), and 18 collagen amino acids throughout all three interventions. The serum PINP concentration × time area-under-the-curve (AUC) was higher following 30 g (169 ± 28 µg/mL × h) than 15 g (134 ± 23 µg/mL × h, P < 0.05) HC ingestion, and both 15 g and 30 g were higher than 0 g HC (96 ± 23 µg/mL × h, P < 0.05). RE with 0 g HC showed no change in serum PINP concentration. The AUCs for glycine, proline, hydroxyproline, alanine, arginine, lysine, serine, leucine, valine, and isoleucine were greater with 30 g than 15 g and 0 g HC ingestion (P < 0.05) and greater with 15 g than 0 g HC ingestion (P < 0.05). Plasma β-CTx concentration decreased after RE independently of HC dose. Our study suggests connective tissue anabolic resistance to RE in middle-aged men but ingesting 15 g HC rescues the collagen synthesis response and 30 g augments that response further. This dose response is associated with the increased bioavailability of collagen amino acids in the blood, which stimulate collagen synthesis.NEW & NOTEWORTHY This study is the first to document the dose-response effect of hydrolyzed collagen (HC) ingestion before resistance exercise (RE) on collagen turnover in middle-aged, resistance-trained men. Strikingly, RE alone did not increase collagen synthesis (suggesting connective tissue anabolic resistance), but ingesting 15 g HC rescued the collagen synthesis response and 30 g augmented that response further. These results were associated with the increased bioavailability of collagen amino acids in the blood, which stimulate collagen synthesis.