Tendon Collagen Synthesis Research Articles

The Collagen Synthesis Response to an Acute Bout of Resistance Exercise Is Greater when Ingesting 30 g Hydrolyzed Collagen Compared with 15 g and 0 g in Resistance-Trained Young Men

BackgroundResistance exercise (RE) stimulates collagen synthesis in skeletal muscle and tendon but there is limited and equivocal evidence regarding an effect of collagen supplementation and exercise on collagen synthesis. Furthermore, it is not known if a dose–response exists regarding the effect of hydrolyzed collagen (HC) ingestion and RE on collagen synthesis. ObjectiveTo determine the HC dose–response effect on collagen synthesis after high-intensity RE in resistance-trained young men. MethodsUsing a double-blind, randomized crossover design, 10 resistance-trained males (age: 26 ± 3 y; height: 1.77 ± 0.04 m; mass: 79.7 ± 7.0 kg) ingested 0 g, 15 g, or 30 g HC with 50 mg vitamin C 1 h before performing 4 sets’ barbell back squat RE at 10-repetition maximum load, after which they rested for 6 h. Blood samples were collected throughout each of the 3 interventions to analyze procollagen type Ⅰ N-terminal propeptide (PINP) and β-isomerized C-terminal telopeptide of type I collagen (β-CTX) concentration, and the concentration of 18 collagen amino acids. ResultsThe serum PINP concentration × time area under the curve (AUC) was greater for 30 g (267 ± 79 μg·L−1·h) than for 15 g (235 ± 70 μg·L−1·h, P = 0.013) and 0 g HC (219 ± 88 μg·L−1·h, P = 0.002) but there was no difference between 0 and 15 g HC (P = 0.225). The AUCs of glycine and proline were greater for 30 g than for 15 and 0 g HC (P < 0.05). Plasma β-CTX concentration decreased from −1 to +6 h (P < 0.05), with no differences between interventions. ConclusionsIngesting 30 g HC before high-intensity RE augments whole-body collagen synthesis more than 15 g and 0 g HC in resistance-trained young males.

Anterior cruciate ligament remnant preservation attenuates apoptosis and enhances the regeneration of hamstring tendon graft

The effects of remnant preservation on the anterior cruciate ligament (ACL) and its relationship with the tendon graft remain unclear. We hypothesized that the co-culture of remnant cells and bone marrow stromal cells (BMSCs) decreases apoptosis and enhances the activity of the hamstring tendons and tenocytes, thus aiding ACL reconstruction. The ACL remnant, bone marrow, and hamstring tendons were surgically harvested from rabbits. The apoptosis rate, cell proliferation, and expression of types I and III collagen, transforming growth factor-β (TGF-β), vascular endothelial growth factor (VEGF), and tenogenic genes (scleraxis (SCX), tenascin C (TNC), and tenomodulin (TNMD)) of the hamstring tendons were compared between the co-culture medium (ACL remnant cells (ACLRCs) and BMSCs co-culture) and control medium (BMSCs-only culture). We also evaluated the apoptosis, cell proliferation, migration, and gene expression of hamstring tenocytes with exposure to co-culture and control media. Compared to BMSCs-only culture medium, the co-culture medium showed substantially decreased early and late apoptosis rates, attenuation of intrinsic and extrinsic apoptotic pathways, and enhanced proliferation of the hamstring tendons and tenocytes. In addition, the expression of collagen synthesis, TGF-β, VEGF, and tenogenic genes in the hamstring tendons and tenocytes significantly increased in the co-culture medium compared to that in the control medium. In the presence of ACLRCs and BMSCs, the hamstring tendons and tenocytes significantly attenuated apoptosis and enhanced the expression of collagen synthesis, TGF-β, VEGF, and tenogenic genes. This in vitro study suggests that the ACLRCs mixed with BMSCs could aid regeneration of the hamstring tendon graft during ACL reconstruction.Cite this article: Bone Joint Res2023;12(1):9-21.

No Treatment Benefits of Local Administration of Insulin-like Growth Factor-1 in Addition to Heavy Slow Resistance Training in Tendinopathic Human Patellar Tendons: A Randomized, Double-Blind, Placebo-Controlled Trial With 1-Year Follow-up

Background: Heavy slow resistance (HSR) training is currently recommended as part of the treatment of patellar tendon tendinopathy. However, treatment success is not reached in all patients, and combinations of different treatments could be beneficial. Local administration of insulin-like growth factor-1 (IGF-1) in humans has been shown to quickly stimulate tendon collagen synthesis. Purpose: To study whether IGF-1 injections combined with HSR training enhance tendon synthesis, tissue structure, and patient satisfaction versus saline injection combined with HSR training in patients with patellar tendinopathy. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Forty patients (age 18-50 years) with unilateral patellar tendinopathy undertook HSR training (3 times a week for 12 weeks) and received intratendinous IGF-1 injections (1 mg IGF-1 per dose) or isotonic saline injections (sham injections) at baseline and after 1 and 2 weeks of training. The primary outcome was collagen synthesis parameters after 12 weeks (primary endpoint). The secondary outcomes were patient-reported outcomes (scores on the Victorian Institute of Sport Assessment–Patella [VISA-P] and visual analog scale [VAS] for pain) and structural changes before the initiation of treatment and at week 3, week 12, and 1 year after the initiation of treatment. Results: Analysis of the patellar tendon biopsy specimens at 12 weeks showed that collagen mRNA and total RNA were increased in the tendinopathic tendons compared with the contralateral healthy tendons regardless of treatment with IGF-1 or saline. Similarly, no difference between the groups was seen in tendon thickness and Doppler activity at week 12 or at 1-year follow-up. The combination of HSR training and IGF-1 injections significantly improved VISA-P and VAS pain scores after 3 weeks, whereas the overall responses after 12 weeks and at 1-year follow-up were identical in the 2 groups. Conclusion: Although a small, immediate clinical response to IGF-1 injections was seen when combined with training, no additional long-term effect of intratendinous IGF-1 was observed on structural and clinical outcomes in patients with patellar tendinopathy. Registration: NCT01834989 (ClinicalTrials.gov identifier)

Swimming exercise changed the collagen synthesis and calcification in calcaneal tendons of mice.

Obesity is characterized by the excess of body fat and, therefore, may cause musculoskeletal alterations that can negatively influence the tendons. Such overweight-influenced alterations are exercise sensitive though. Morphological and biochemical alterations were reported in the calcaneal tendon of mice submitted to a lipid-rich diets along with practicing exercises, with the following groups: normal diet without exercise (ND), normal diet with exercise (NDex), lipid-rich diet without exercise (LD), lipid-rich diet without exercise (LDex). The calcaneal tendons were removed and subjected to histological and biochemical analysis. Layers of the tissue were stained with Hematoxylin and Eosin, Picrosirius Red and Von Kossa while a protein dosage was conduce by the Bradford method. The morphologicals analysis there was no statistical difference concerning the number of fibroblasts among the groups. Groups submitted to exercises showed higher amount of collagen and non-collagenous protein deposition. The lipid-rich diet without exercse group had a more disorganized collagen matrix with intense basophilia. The same group had areas of calcification confirmed by Von Kossa technique. Practicing physical activity, such as swimming, can improve the changes caused in the calcaneal tendon in mice submitted to a lipid-rich diets, having a better collagen organization and the synthesis.

Influence of Oral Contraceptive Use on Adaptations to Resistance Training.

Introduction: The majority of young women use oral contraceptives (OCs). Use of OCs has been associated with lower myofibrillar protein and tendon collagen synthesis rates, but it is unknown whether OCs will limit the adaptive response of myotendinous tissue to resistance training.Design and Methods: Fourteen healthy untrained young regular OC users (24 ± 1 years, fat% 32 ± 1, 35 ± 2 ml⋅min-1⋅kg-1) and 14 NOC users (non-OC, controls) (24 ± 1 years, fat% 32 ± 2, 34 ± 2 ml⋅min-1⋅kg-1) performed a 10-week supervised lower extremity progressive resistance training program. Before and after the intervention biopsies from the vastus lateralis muscle and the patellar tendon were obtained. Muscle (quadriceps) and tendon cross-sectional area (CSA) was determined by magnetic resonance imaging (MRI) scans, and muscle fiber CSA was determined by histochemistry. Maximal isometric knee extension strength was assessed by dynamometry while 1 repetition maximum (RM) was determined during knee extension.Results: Training enhanced CSA in both muscle (p < 0.001) and tendon (p < 0.01). A trend toward a greater increase in muscle CSA was observed for OC (11%) compared to NOC (8%) (interaction p = 0.06). Analysis of mean muscle fiber type CSA showed a trend toward an increase in type II muscle fiber area in both groups (p = 0.11, interaction p = 0.98), whereas type I muscle fiber CSA increased in the OC group (n = 9, 3821 ± 197 to 4490 ± 313 mm2, p < 0.05), but not in NOC (n = 7, 4020 ± 348 to 3777 ± 354 mm2, p = 0.40) (interaction p < 0.05). Post hoc analyses indicated that the effect of OCs on muscle mass increase was induced by the OC-users (n = 7), who used OCs containing 30 μg ethinyl estradiol (EE), whereas the response in users taking OCs with 20 μg EE (n = 7) did not differ from NOC. Both the OC and NOC group experienced an increase in maximal knee strength (p < 0.001) and 1RM leg extension (p < 0.001) after the training period with no difference between groups.Conclusion: Use of OCs during a 10-week supervised progressive resistance training program was associated with a trend toward a greater increase in muscle mass and a significantly greater increase in type I muscle fiber area compared to controls. Yet, use of OCs did not influence the overall increase in muscle strength related to training.

Importance of the circadian clock in tendon development.

Tendons are remarkable tissues that transmit force from muscle to bone during joint movement. They are remarkable because they withstand tensile forces that are orders of magnitude greater than can be withstood by isolated cells. The ability of the cells to survive is directly attributable to the stress shielding properties of the collagen-rich extracellular matrix of the tissue. A further remarkable feature is that the vast majority (>98%) of the collagen is never turned over; it is synthesized during embryonic through early adult development and persists for the lifetime of the person. How the collagen is synthesized, and importantly, how it is protected from fatigue failure for decades of countless loading cycles, remains a mystery. A recent discovery is that tendons are peripheral circadian clock tissues in which the expression of ~5% of the transcriptome is rhythmic during 24h. Evidence is emerging that a fraction of the total amount of collagen is synthesized and removed on a daily basis without being incorporated into the lifelong permanent collagen. This review provides some of the background, and summarizes the findings, of these latest discoveries. Detailed descriptions of tendon development, collagen synthesis and collagen fibrillogenesis can be found in excellent reviews (cited here) and will not be a major part of this review.

ER\u03b1 PvuII and XbaI polymorphisms in postmenopausal women with posterior tibial tendon dysfunction: a case control study

BackgroundPosterior tibial tendon (PTT) insufficiency is considered as the main cause of adult acquired flat foot and is three times more frequent in females. High estrogen levels exert a positive effect on the overall collagen synthesis in tendons. We have previously demonstrated the association between some genetic single-nucleotide polymorphism (SNP) and tendinopathy. In the present study, we investigated the association of PvuII c454-397T>C (NCBI ID: rs2234693) and XbaI c454-351A>G (NCBI ID: rs9340799) SNPs in estrogen receptor alfa (ER-α) gene with PPT dysfunction.MethodsA total of 92 female subjects with PTT dysfunction, with histopathological examination of the tendon and magnetic resonance image (MRI) evidence of tendinopathy, were compared to 92 asymptomatic females who presented an intact PPT at MRI for PvuII and XbaI SNPs in the ER-α gene. Genomic DNA was extracted from saliva and genotypes were obtained by polymerase chain reaction restriction fragment length polymorphism.ResultsThe analysis of PvuII SNPs showed no significant differences in the frequency of alleles and genotypes between control and PTT dysfunction groups. The XbaI SNPs in the ER-α gene showed significant differences in the frequency of genotypes between control and test groups (p = 0.01; OR 95% 1.14 (0.55–2.33).ConclusionsThe XbaI SNP in the ERα gene may contribute to tendinopathy, and the A/A genotype could be a risk factor for PTT tendinopathy in this population. The PvuII SNP studied was not associated with PTT tendinopathy.

Tendon Pathology: Have we missed the first step in the development of pathology?

Tendon Pathology: Have we missed the first step in the development of pathology?

The influence of chronic IL-6 exposure, in vivo, on rat Achilles tendon extracellular matrix

When compared to placebo, acetaminophen (APAP) reduces tendon stiffness and collagen cross-linking. APAP also enhances the exercise-induced increase in peritendinous levels of IL-6. Elevated levels of IL-6 are associated with tendinopathy, thus we hypothesized that chronic, elevated peritendinous IL-6 would alter tendon extracellular matrix (ECM). IL-6 (∼3000pgml−1) was injected (3dwk−1 for 8-wks) into the Achilles peritendinous region of male Wistar rats (n=16) with the opposite leg serving as a sham. Fractional synthesis rates (FSR) were determined using deuterium oxide. Collagen (hydroxyproline) and hydroxylysl pyridinoline (HP) cross-linking were analyzed by HPLC. ECM and IL-6 related genes were evaluated using qRT-PCR. Relative to sham, collagen (Col) 1a1 but not Col3a1 expression was suppressed (47%) in tendons exposed to IL-6 (p<0.05). Lysyl oxidase (LOX) and MMP-1 expression were also reduced (37%) in IL-6 treated tendons (p<0.05). Relative to sham the expression of MMP-2, -3, -9, and TIMP-1 were not altered by IL-6 treatment (p>0.05). Interleukin-6 receptor subunit beta precursor (IL6st) was lower (16%) in IL-6 treated tendons when compared to sham (p<0.05). Suppressor of cytokine signaling 3 (Socs3), signal transducer and activator of transcription 3 (STAT3), and protein inhibitor of activated STAT 1 (Pias1) were not altered by IL-6 exposure (p>0.05). Neither collagen nor cross-linking content were altered by IL-6 (p>0.05). Additionally, IL-6 treatment did not alter tendon FSR. Chronic treatment with physiologically relevant levels of IL-6 suppresses expression of Col1a1 and LOX while also altering expression of select MMPs but does not alter Achilles tendon collagen synthesis.

Tendon collagen synthesis declines with immobilization in elderly humans: no effect of anti-inflammatory medication.

In elderly humans, 2 wk of inactivity reduces tendon collagen protein synthesis, while tendon stiffness and modulus are only marginally reduced, and NSAID treatment does not affect this. This indicates that mechanical loading is important for maintenance of tendon collagen turnover and that changes in collagen turnover induced by short-term immobilization may only have minor impact on the internal structures that are essential for mechanical properties in elderly tendons.

Sex-based difference in Achilles peritendinous levels of matrix metalloproteinases and growth factors after acute resistance exercise.

Several recent investigations have demonstrated that the ability of various tendons to alter structural and functional properties in response to exercise are muted in women compared with men. We hypothesize that this disparity between men and women may be due to a reduced tendon production of key mediators of tendon extracellular matrix (ECM) remodeling in response to mechanical loading, e.g., exercise. Using microdialysis before and after an acute bout of resistance exercise, we evaluated Achilles peritendinous levels of insulin-like growth factor-1 (IGF-1) and interleukin-6 (IL-6), which have both been shown to increase tendon collagen synthesis. Additionally, the matrix remodeling enzymes matrix metalloproteinase-2 (MMP-2), MMP-9, and tissue inhibitor of metalloproteinase-1 (TIMP-1) were also evaluated. IGF-1 levels were elevated (P < 0.05) to a similar extent in men and women after 3 h of exercise but remained elevated at 4 h in only women. IL-6 levels were ~4-fold greater after exercise in both men and women (P < 0.05). MMP-2 levels increased to a similar extent (~2-3-fold) in men and women (P < 0.05). In contrast, MMP-9 increased with exercise but only in men (P < 0.05). Last, TIMP-1 levels also increased (P < 0.05) with exercise in men and women but the increase was more prolonged in women. In conclusion, we observed modest sex differences in tendon release of MMP-9, TIMP-1, and IGF-1 after acute resistance exercise. If such differences persist throughout a chronic exercise training, they may contribute to the reduced ability of women to adapt to exercise compared with men.NEW & NOTEWORTHY In this investigation we utilized microdialysis of the peritendinous Achilles to evaluate potential differences between men and women in tendon production of key regulators of extracellular matrix remodeling. We demonstrate that a modest sex-specific difference exists in peritendinous levels of several key extracellular matrix modulators after an acute bout of resistance exercise.

Effect of aging and exercise on the tendon.

Here, we review the literature on how tendons respond and adapt to ageing and exercise. With respect to aging, there are considerable changes early in life, but this seems to be maturation rather than aging per se. In vitro data indicate that aging is associated with a decreased potential for cell proliferation and a reduction in the number of stem/progenitor-like cells. Further, there is persuasive evidence that turnover in the core of the tendon after maturity is very slow or absent. Tendon fibril diameter, collagen content, and whole tendon size appear to be largely unchanged with aging, while glycation-derived cross-links increase substantially. Mechanically, aging appears to be associated with a reduction in modulus and strength. With respect to exercise, tendon cells respond by producing growth factors, and there is some support for a loading-induced increase in tendon collagen synthesis in humans, which likely reflects synthesis at the very periphery of the tendon rather than the core. Average collagen fibril diameter is largely unaffected by exercise, while there can be some hypertrophy of the whole tendon. In addition, it seems that resistance training can yield increased stiffness and modulus of the tendon and may reduce the amount of glycation. Exercise thereby tends to counteract the effects of aging.

Collagen Homeostasis and Metabolism.

The musculoskeletal system and its collagen rich tissue is important for ensuring architecture of skeletal muscle, energy storage in tendon and ligaments, joint surface protection, and for ensuring the transfer of muscular forces into resulting limb movement. Structure of tendon is stable and the metabolic activity is low, but mechanical loading and subsequent mechanotransduction and molecular anabolic signaling can result in some adaptation of the tendon especially during youth and adolescence. Within short time, tendon will get stiffer with training and lack of mechanical tissue loading through inactivity or immobilization of the human body will conversely result in a dramatic loss in tendon stiffness and collagen synthesis. This illustrates the importance of regular mechanical load in order to preserve the stabilizing role of the connective tissue for the overall function of the musculoskeletal system in both daily activity and exercise. Adaptive responses may vary along the tendon, and differ between mid-substance and insertional areas of the tendon.

Sex Hormones and Tendon.

The risk of overuse and traumatic tendon and ligament injuries differ between women and men. Part of this gender difference in injury risk is probably explained by sex hormonal differences which are specifically distinct during the sexual maturation in the teenage years and during young adulthood. The effects of the separate sex hormones are not fully elucidated. However, in women, the presence of estrogen in contrast to very low estrogen levels may be beneficial during regular loading of the tissue or during recovering after an injury, as estrogen can enhance tendon collagen synthesis rate. Yet, in active young female athletes, physiological high concentration of estrogen may enhance the risk of injuries due to reduced fibrillar crosslinking and enhanced joint laxity. In men, testosterone can enhance tendon stiffness due to an enhanced tendon collagen turnover and collagen content, but testosterone has also been linked to a reduced responsiveness to relaxin. The present chapter will focus on sex difference in tendon injury risk, tendon morphology and tendon collagen turnover, but also on the specific effects of estrogen and androgens.

P38 MAPK signaling in postnatal tendon growth and remodeling.

Tendon is a dynamic tissue whose structure and function is influenced by mechanical loading, but little is known about the fundamental mechanisms that regulate tendon growth and remodeling in vivo. Data from cultured tendon fibroblasts indicated that the p38 MAPK pathway plays an important role in tendon fibroblast proliferation and collagen synthesis in vitro. To gain greater insight into the mechanisms of tendon growth, and explore the role of p38 MAPK signaling in this process, we tested the hypotheses that inducing plantaris tendon growth through the ablation of the synergist Achilles tendon would result in rapid expansion of a neotendon matrix surrounding the original tendon, and that treatment with the p38 MAPK inhibitor SB203580 would prevent this growth. Rats were treated with vehicle or SB203580, and subjected to synergist ablation by bilateral tenectomy of the Achilles tendon. Changes in histological and biochemical properties of plantaris tendons were analyzed 3, 7, or 28 days after overload, and comparisons were made to non-overloaded animals. By 28 days after overload, tendon mass had increased by 30% compared to non-overloaded samples, and cross-sectional area (CSA) increased by around 50%, with most of the change occurring in the neotendon. The expansion in CSA initially occurred through the synthesis of a hyaluronic acid rich matrix that was progressively replaced with mature collagen. Pericytes were present in areas of active tendon growth, but never in the original tendon ECM. Inhibition of p38 MAPK resulted in a profound decrease in IL6 expression, and had a modest effect on the expression of other ECM and cell proliferation genes, but had a negligible impact on overall tendon growth. The combined results from this study provided novel insights into tendon mechanobiology, and suggest that p38 MAPK signaling does not appear to be necessary for tendon growth in vivo.

The Muscle Stretch Reflex throughout the Menstrual Cycle

The significant sex disparity in sports-related knee injuries may be due to underlying differences in motor control. Although the development of sex-specific movement patterns is likely multifactorial, this study specifically focuses on the potential modulatory role of sex hormones. This study aimed to investigate the muscle stretch reflex (MSR) across the menstrual cycle. We hypothesized that the MSR would fluctuate throughout the menstrual cycle and that the lowest response would correspond with peak concentrations of estrogen. Nineteen healthy women age 18-35 yr participated in this study: 8 eumenorrheic women and 11 women taking oral contraceptives. Serum estradiol and progesterone concentrations, anterior knee laxity (AKL), and the MSR response of the quadriceps muscles were measured three times during the menstrual cycle. The MSR response of the rectus femoris (RF) varied significantly across the menstrual cycle in both groups. Specifically, the RF MSR response was 2.4 times lower during the periovulatory phase when compared with the luteal phase (P = 0.007). The same trend was seen in the vastus medialis, but this did not reach statistical significance (P = 0.070). The MSR response of the vastus lateralis did not change significantly across the menstrual cycle (P = 0.494). A mixed model comparison did not show an association between endogenous concentrations of estradiol and progesterone, exposure to hormonal contraceptives or AKL, and the MSR response for any muscle. Our results demonstrate that the RF MSR response varies throughout the menstrual cycle with the lowest response around the time of ovulation. Additional research is needed to clarify the exact relationship between sex hormones, AKL, and MSR response and to determine the specific origin of the change along the monosynaptic reflex arc.

Local administration of growth hormone stimulates tendon collagen synthesis in elderly men

Tendon collagen content and circulating growth hormone (GH) are reduced in elderly. In a placebo-controlled, double-blinded study, we examined if local injections of rhGH enhance collagen synthesis in healthy elderly men (61 ± 1 yr). Two injections of rhGH or saline (control) were injected into each of the patient's patellar tendons, respectively. Subsequently, tendon collagen fractional synthesis rate (FSR) and an indirect marker of type I collagen synthesis (PINP) were measured. Within the first 6 h after the last injections, a tendency towards a higher tendon collagen FSR was observed in 10 out of 12 subjects (P = 0.08). Similarly, PINP was higher 3-4 h after the last GH injection (P = 0.05). Serum IGF-I did not change from baseline, whereas peritendinous bioactive IGF-I was higher in the GH leg vs. control (P = 0.05). In conclusion, local injections of rhGH increase tendon collagen synthesis in humans, either directly or indirectly by increasing local bioactive IGF-I.

Effects of transdermal estrogen on collagen turnover at rest and in response to exercise in postmenopausal women

Menopause is associated with loss of collagen content in the skin and tendon as well as accumulation of noncontractile tissue in skeletal muscle. The relative role of hormones and physical activity on these changes is not known. Accordingly, in a randomized, controlled, crossover study we investigated effects of transdermal estrogen replacement therapy (ERT) on type I collagen synthesis in tendon and skeletal muscle in 11 postmenopausal women. Patches with estrogen (Evorel) were placed on the skin above the patellar tendons and compared with no patch (control period). On day 2 all subjects performed one-legged exercise, and thereafter the exercised leg (EX leg) was compared with the nonexercised leg (Rest leg). Microdialysis catheters were placed in front of the patellar tendons and in the vastus lateralis muscle of both legs at days 3 and 5. The collected dialysate was analyzed for procollagen type I NH(2)-terminal propeptide (PINP), insulin-like growth factor I (IGF-I), and interleukin-6 (IL-6). Neither loading (Rest leg vs. EX leg) nor treatment (control vs. ERT) influenced peritendinous PINP, whereas combined exercise and ERT enhanced muscle PINP after 72 h (interaction between loading and treatment P = 0.008). In neither skeletal muscle nor peritendinous fluid were IGF-I and IL-6 influenced by treatment or exercise. In conclusion, ERT was associated with enhanced synthesis of type I collagen in the skeletal muscle in response to acute exercise. In perspective, this indicates that the availability of estrogen in postmenopausal women is important for repair of muscle damage or remodeling of the connective tissue within the skeletal muscle after exercise.

Changes in Bone Alkaline Phosphatase and Procollagen Type-1 C-Peptide After Static and Dynamic Exercises

We investigated the effects of two types of nonweight-bearing exercise on changes in bone-specific alkaline phosphatase (BAP) and procollagen type 1 C-peptide (P1P). BAP is a specific marker of bone synthesis, whereas P1P reflects synthesis of type 1 collagen in other organs as well as bone. Eight participants performed static and dynamic unilateral knee extensions. BAP and P1P were measured before, and at 1, 2, 24, 48, and 72 hr after exercise. P1P increased at 24 hr after a static knee extension exercise, whereas BAP did not change during the experimental period. We found no changes in these markers after dynamic exercise. These results imply that type 1 collagen synthesis in tendons increases after static exercise.

Local administration of insulin‐like growth factor‐I(IGF‐I) stimulates tendon collagen synthesis in humans

Collagen is the predominant structural protein in tendons and ligaments, and can be controlled by hormonal changes. In animals, injections of insulin-like growth factor I (IGF-I) has been shown to increase collagen synthesis in tendons and ligaments and to improve structural tissue healing, but the effect of local IGF-I administration on tendon collagen synthesis in human has not been studied. The purpose of this study was to study whether local injections of IGF-I would have a stimulating effect on tendon collagen synthesis. Twelve healthy nonsmoking men [age 62 ± 1 years (mean ± SEM), BMI 27 ± 1] participated. Two injections of either human recombinant IGF-I (0.1 mL Increlex©) or saline (control) into each patellar tendon were performed 24-h apart, respectively. Tendon collagen fractional synthesis rate (FSR) was measured by stable isotope technique in the hours after the second injection. Simultaneously, interstitial peritendinous (IGF-I) and [procollagen type I N-terminal propeptide (PINP)], as a marker for type I collagen synthesis, were determined by microdialysis technique. Tendon collagen FSR and PINP were significantly higher in the IGF-I leg compared with the control leg (P < 0.05). In conclusion, local IGF-I administration can directly enhance tendon collagen synthesis both within and around the human tendon tissue.