Relationship between extensibility and collagen expression in immobilized rat skeletal muscle.

INTRODUCTION: This study investigated longitudinal changes in muscle extension and collagen expression in an immobilized rat soleus muscle, and assessed the relationship between both elements. METHODS: Soleus muscles of the control and immobilization groups (1, 2, 4, 8, and 12 weeks) were used for analysis of muscle extensibility and collagen expression. RESULTS: The slope value/physiological cross-sectional area (PCSA; a parameter for muscle extensibility) and hydroxyproline (a parameter for collagen expression) were significantly higher in the immobilization group than in the control group for all experimental time points. In the immobilization group, both factors were significantly higher at 4, 8, and 12 weeks than at 1 and 2 weeks after immobilization. A significant positive correlation was observed between the slope value/PCSA and hydroxyproline expression. DISCUSSION: The present study indicated that a decrease in muscle extensibility depended on collagen overexpression in immobilized rat soleus muscles. Muscle Nerve 57: 672-678, 2018.

Development and progression of immobilization-induced skin fibrosis through overexpression of transforming growth factor-ß1 and hypoxic conditions in a rat knee joint contracture model.

PURPOSE: The purpose of this study was to investigate the pathology and mechanism of immobilization-induced skin fibrosis in a rat joint contracture model. METHODS: Rats were randomly divided into control and immobilization groups. In the immobilization groups, knee joints of the rats were immobilized for 1, 2, and 4 weeks. After each immobilization, skin was dissected. To assess fibrosis in the skin, the thickness and area of adipocytes and connective tissue fibers were measured. Myofibroblasts were analyzed by immunohistochemistry by using anti-α-SMA as a marker. Gene expression levels of type I and III collagen, TGF-ß1, and HIF-1α were measured by using RT-PCR. RESULTS: One week after immobilization, there was a marked increase in the area of connective tissue fibers in the immobilization group. Type I and type III collagen were significantly increased with prolonged immobilization. Higher numbers of α-SMA-positive cells were noted in the immobilized group at 2 and 4 weeks after immobilization. The expression level of TGF-ß1 mRNA in the immobilization group increased after one week of immobilization. In contrast, the expression level of HIF1-α mRNA increased after 2 weeks of immobilization, and a greater increase was seen at 4 weeks after immobilization. CONCLUSIONS: These results suggest that immobilization induces skin fibrosis with accumulation of types I and III collagen. These fibrotic changes may be evoked by upregulation of TGF-ß1 after one week of immobilization. Additionally, upregulation of HIF-1α may relate to skin fibrosis by accelerating the differentiation of fibroblasts to myofibroblasts starting at 2 weeks after immobilization.

Upregulation of interleukin-1ß/transforming growth factor-ß1 and hypoxia relate to molecular mechanisms underlying immobilization-induced muscle contracture.

INTRODUCTION: In this study we investigated the molecular mechanism underlying muscle contracture in rats. METHODS: The rats were divided into immobilization and control groups, and soleus muscles of the right and left sides were selected for analyses. RESULTS: The levels of CD11b and α-SMA protein, IL-1ß, and TGF-ß1 mRNA, and type I and III collagen protein and mRNA were significantly greater in the immobilization group than in the control group at all time-points. HIF-1α mRNA levels were significantly higher in the immobilization group at 4 weeks. Moreover, HIF-1α, α-SMA, and type I collagen levels were significantly higher at 4 weeks than at 1 and 2 weeks in the immobilization group. CONCLUSIONS: In the early stages of immobilization, upregulation of IL-1ß/TGF-ß1 via macrophages may promote fibroblast differentiation that could affect muscle contracture. The soleus muscle became hypoxic in the later stages of immobilization, suggesting that hypoxia influences the progression of muscle contracture.

Effects of Physical-Agent Pain Relief Modalities for Fibromyalgia Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Purpose: We conducted a systematic review and meta-analysis to investigate the effects of the following physical-agent modalities for pain relief in fibromyalgia (FM) patients. Methods: We identified randomized controlled studies of adults with FM in the MEDLINE, CINAHL, and PEDro databases. The primary outcome measure was pain relief measured by a visual analogue scale (VAS), and the secondary outcome measures of interest were subjective improvements in the number of tender points, Fibromyalgia Impact Questionnaire (FIQ), and quality of life (QOL) scores. Results: Eleven studies were included in our review. The studies' physical-agent modalities were low-level laser therapy (LLLT), thermal therapy, electromagnetic field therapy, and transcutaneous electrical nerve stimulation (TENS). LLLT did not reduce VAS scores, but it significantly reduced both the number of tender points and FIQ score. Thermal therapy was associated with significantly reduced VAS scores, tender points, and FIQ scores. Electromagnetic field therapy was associated with significantly reduced VAS score and FIQ score. TENS significantly reduced VAS scores. Conclusion: Our analyses revealed that thermal therapy and LLLT had a partial effect on pain relief in FM patients, and this beneficial effect may have a positive influence on FM patients' health status.

Effects of joint immobilization on changes in myofibroblasts and collagen in the rat knee contracture model.

The purpose of this study was to examine the time-dependent changes in the development of joint capsule fibrosis and in the number of myofibroblasts in the joint capsule after immobilization, using a rat knee contracture model. Both knee joints were fixed in full flexion for 1, 2, and 4 weeks (immobilization group). Untreated rats were bred for each immobilization period (control group). Histological analysis was performed to evaluate changes in the amount and density of collagen in the joint capsule. The changes in type I and III collagen mRNA were examined by in situ hybridization. The number of myofibroblasts in the joint capsule was assessed by immunohistochemical methods. In the immobilization group, the amount of collagen increased within 1 week and the density of collagen increased within 2 weeks, as compared with that in the control group. Type I collagen mRNA-positive cell numbers in the immobilization group increased at all time points. However, type III collagen mRNA-positive cell numbers did not increase. Myofibroblasts in the immobilization group significantly increased compared with those in the control group at all time points, and they increased significantly with the period of immobilization. These results suggest that joint capsule fibrosis with overexpression of type I collagen occurs and progresses within 1 week after immobilization, and an increase in myofibroblasts is related to the mechanism of joint capsule fibrosis. The findings suggest the need for a treatment targeting accumulation of type I collagen associated with an increase in myofibroblasts. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1998-2006, 2017.