Dual effects of TGF-ß inhibitor in ALS - inhibit contracture and neurodegeneration.

As persistent elevation of transforming growth factor-ß (TGF-ß) promotes fibrosis of muscles and joints and accelerates disease progression in amyotrophic lateral sclerosis (ALS), we investigated whether inhibition of TGF-ß would be effective against both exacerbations. The effects of TGF-ß and its inhibitor on myoblasts and fibroblasts were tested in vitro and confirmed in vivo, and the dual action of a TGF-ß inhibitor in ameliorating the pathogenic role of TGF-ß in ALS mice was identified. In the peripheral neuromuscular system, fibrosis in the muscles and joint cavities induced by excessive TGF-ß causes joint contracture and muscular degeneration, which leads to motor dysfunction. In an ALS mouse model, an increase in TGF-ß in the central nervous system (CNS), consistent with astrocyte activity, was associated with M1 microglial activity and pro-inflammatory conditions, as well as with neuronal cell death. Treatment with the TGF-ß inhibitor halofuginone could prevent musculoskeletal fibrosis, resulting in the alleviation of joint contracture and delay of motor deterioration in ALS mice. Halofuginone could also reduce glial cell-induced neuroinflammation and neuronal apoptosis. These dual therapeutic effects on both the neuromuscular system and the CNS were observed from the beginning to the end stages of ALS; as a result, treatment with a TGF-ß inhibitor from the early stage of disease delayed the time of symptom exacerbation in ALS mice, which led to prolonged survival.

Bone marrow-derived fibroblast migration via periostin causes irreversible arthrogenic contracture after joint immobilization.

Joint contracture causes distressing permanent mobility disorder due to trauma, arthritis, and aging, with no effective treatment available. A principal and irreversible cause of joint contracture has been regarded as the development of joint capsule fibrosis. However, the molecular mechanisms underlying contracture remain unclear. We established a mouse model of knee joint contracture, revealing that fibrosis in joint capsules causes irreversible contracture. RNA-sequencing of contracture capsules demonstrated a marked enrichment of the genes involved in the extracellular region, particularly periostin (Postn). Three-dimensional magnetic resonance imaging and immunohistological analysis of contracture patients revealed posterior joint capsule thickening with abundant type I collagen (Col1a2) and POSTN in humans. Col1a2-GFPTG ; Postn-/- mice and chimeric mice with Col1a2-GFPTG ; tdTomatoTG bone marrow showed fibrosis in joint capsules caused by bone marrow-derived fibroblasts, and POSTN promoted the migration of bone marrow-derived fibroblasts, contributing to fibrosis and contracture. Conversely, POSTN-neutralizing antibody attenuated contracture exacerbation. Our findings identified POSTN as a key inducer of fibroblast migration that exacerbates capsule fibrosis, providing a potential therapeutic strategy for joint contracture.

Joint contractures is a recurrent clinical feature of individuals with neurodevelopmental disorder due to FOXP1 likely gene disruptive variants.

Haploinsufficiency of FOXP1 gene is responsible for a neurodevelopmental disorder presenting with intellectual disability (ID), autism spectrum disorder (ASD), hypotonia, mild dysmorphic features, and multiple congenital anomalies. Joint contractures are not listed as a major feature of FOXP1-related disorder. We report five unrelated individuals, each harboring likely gene disruptive de novo FOXP1 variants or whole gene microdeletion, who showed multiple joint contractures affecting at least two proximal and/or distal joints. Consistent with the phenotype of FOXP1-related disorder, all five patients showed developmental delay with moderate-to-severe speech delay, ID, ASD, and facial dysmorphic features. FOXP1 is implicated in neuronal differentiation and in organizing motor axon projections, thus providing a potential developmental basis for the joint contractures. The combination of joint contractures and neurodevelopmental disorders supports the clinical suspicion of FOXP1-related phenotype.

Long-term effects of non-weight bearing and immobilization after anterior cruciate ligament reconstruction on joint contracture formation in rats.

PURPOSE: Non-weight bearing improves and immobilization worsens contracture induced by anterior cruciate ligament reconstruction (ACLR), but effect persistence after reloading and remobilization remains unclear, and the combined effects of these factors on ACLR-induced contracture are unknown. We aimed to determine 1) whether the effects of short-term (2-week) non-weight bearing or immobilization after ACLR on contracture would be sustained by reloading or remobilization during a 10-week observation period, and 2) how the combination of both interventions compared to the outcome of either alone. METHODS: We divided 88 ACL-reconstructed male rats into four groups: non-intervention, non-weight bearing, joint immobilization, and both interventions. Interventions were performed for 2 weeks, followed by rearing without intervention. Twelve untreated rats were used as controls. At 2, 4, and 12 weeks post-surgery, we assessed range of motion (ROM) and histological changes. RESULTS: ACLR resulted in persistent loss of ROM, accompanied by synovial shortening, capsule thickening, and osteophyte formation. Two weeks of non-weight bearing increased ROM and reduced osteophyte size, but the beneficial effects disappeared within 10 weeks after reloading. Two-week immobilization decreased ROM and facilitated synovial shortening. After remobilization, ROM partially recovered but remained below non-intervention levels at 12 weeks. When both interventions were combined, ROM was similar to immobilization alone. CONCLUSIONS: The beneficial effects of 2-week non-weight bearing on contracture diminished within 10 weeks after reloading. The adverse effects of 2-week immobilization on contracture persisted after 10 weeks of remobilization. The effects of the combined use of both interventions on contracture were primarily determined by immobilization.

Preliminary study of extracorporeal shock wave alleviating joint capsule fibrosis caused by internal bleeding of knee joint in rats.

PURPOSE: Joint contracture is a common disease in clinical practice, joint bleeding is an important factor affecting the progression of joint contracture. This study aimed to explore the effect of extracorporeal shock wave on alleviating joint capsule fibrosis caused by intra-articular hemorrhage in rats. METHODS: Forty two SD rats were randomly divided into seven groups. Perform simple fixation and fixation after blood injection separately. Measure the range of motion of each group's knee joints and calculate the corresponding degree of contraction. Use HE staining and Masson staining to detect the number of anterior joint capsule cells and collagen deposition. Detection of changes in Wnt1, ß-catenin protein expression in joint capsule using Western blotting. RESULTS: Compared to group C, the degree of knee joint contracture in M1 and M2 groups of rats increased, and collagen deposition, cell number and Wnt1, ß-catenin protein expression also increased accordingly. Compared to M1 and M2 groups, the degree of knee contraction in E1 and E2 groups were reduced, while collagen deposition, cell number and Wnt1, ß-catenin protein expression were decreased, and the degree of joint contracture in NR1 and NR2 groups showed no significant improvement. Compared to NR1 and NR2 groups, the degree of knee contraction in E1 and E2 groups were reduced, while collagen deposition, cell number and Wnt1, ß-catenin protein expression were decreased. CONCLUSIONS: Both rat models of knee joint contracture were successful, and joint bleeding can exacerbate joint contracture. Extracorporeal shock waves alleviate joint capsule fibrosis caused by intra-articular bleeding in rats.

A child with Winchester syndrome responding to oral betamethasone and methotrexate.

Winchester syndrome (WS) is a rare genetic disorder with a handful of cases reported to date. We report a 14-year-old male who presented with growth retardation, contracture of left lower limb due to thick indurated skin, hypertrichosis, and bilateral corneal opacity. There was complete improvement in joint contracture with oral betamethasone pulse and weekly oral methotrexate.

The effects of weight bearing after ACL reconstruction on joint contracture in rats.

PURPOSE: Joint contractures after anterior cruciate ligament (ACL) reconstruction are a serious problem. Given the uncertain effects of weight bearing after ACL reconstruction on contractures, this study was conducted to examine such effects. MATERIALS AND METHODS: To control the amount of weight bearing, ACL-reconstructed rats were reared with either untreated (small weight bearing; weight bearing during locomotion was 54% of pre-surgery at minimum), hindlimb unloading (non-weight bearing), or sustained morphine administration (large weight bearing; weight bearing during locomotion was maintained at 80% or more of pre-surgery) conditions. Untreated rats were used as controls. Knee extension range of motions (ROMs) before (includes myogenic and arthrogenic factors) and after myotomy (includes arthrogenic factor only) and fibrotic reactions in the joint capsule were assessed 7 and 14 days post-surgery. RESULTS: ACL reconstruction significantly reduced ROMs both before and after myotomy and induced fibrosis in the joint capsule accompanying upregulation of fibrosis-related genes (i.e., type I and III collagens and transforming growth factor-ß1) at both time points. Morphine administration increased the ROM before myotomy, but not after myotomy 7 days post-surgery. Unloading after ACL reconstruction improved ROMs both before and after myotomy at both time points. In addition, unloading after ACL reconstruction attenuated fibrotic reactions in the joint capsule. CONCLUSIONS: Our results suggest that morphine administration improves myogenic contractures in parallel with an increase in the amount of weight bearing. Unloading after ACL reconstruction is effective in reducing both myogenic and arthrogenic contractures.

The effect of extracorporeal shock wave on joint capsule fibrosis in rats with knee extension contracture: a preliminary study.

The purpose of this study was to observe the therapeutic effect of extracorporeal shock wave (ESW) on extensional joint contracture of knee joint in rats and its mechanism on articular capsule fibrosis. Thirty-two SD rats were randomly divided into blank control, immobilization, natural recovery, and ESW intervention groups. Except for the control group, the left knee joints of other rats were fixed with external fixation brace for 4 weeks when they were fully extended to form joint contracture. The effect of intervention was assessed by evaluating joint contracture, total cell count and collagen deposition in joint capsule, and protein expression levels of TGF-ß1, p-Smad2/3, Smad2/3, p-JNK, JNK, I and III collagen in joint capsule. ESW can effectively reduce arthrogenic contracture, improve the histopathological changes of anterior joint capsule, inhibit the high expression of target protein and the excessive activation of TGF-ß1/Smad2/3/JNK signal pathway. Inhibition of excessive activation of TGF-ß1/Smad2/3/JNK pathway may be one of the potential molecular mechanisms by which extracorporeal shock wave can play a role.

[Surgical treatment of combined injuries of the neck and shoulder joints]. / Khirurgicheskoe lechenie sochetannykh porazhenii shei i plechevykh sustavov.

OBJECTIVE: To develop the algorithm for effective surgical restoration of shoulder joint and neck functions and acceleration of social and labor rehabilitation. MATERIAL AND METHODS: There were 116 patients with combined consequences of burns of the neck and shoulder joints between 2012 and 2021. These ones amounted to 29.4% of all patients with lesions of the neck or shoulder joints. Simultaneous surgeries with correction of post-burn cicatricial deformities and contractures were performed in 66 patients (56.9%). Age of patients ranged from 18 to 72 years, and 96% of them were employable. There were 89 (76.7%) women and 27 (23.3%) men. We assessed spread and localization of cicatricial process, as well as restriction of mobility of the neck and shoulder joint to select optimal surgical approach. Classification of neck deformities and contractures of shoulder joints considering severity of cicatricial lesion and functional impairment made it possible to systematize the approach to reconstructive procedures. Reconstructive surgery included repair with local tissues including skin-fatty flap, non-perforated split or full-thickness skin autograft, rotated flaps including those based on perforator vessels, as well as preliminary skin stretching. RESULTS: In general, 116 patients with combined lesions of the neck and shoulder joints underwent 314 surgeries. To accelerate rehabilitation, we performed simultaneous surgeries with correction of deformities and contractures in 66 patients (56.9%). Staged reconstructive surgeries were carried out in 50 patients. Acute dermotension and skin-fatty neck flap grafting were the most common for deformities and contractures of the neck. Skin-fatty axillary flap was used in most patients with contractures of shoulder joints. CONCLUSION: Simultaneous surgeries can accelerate rehabilitation. Correct algorithm of staged surgical treatment reduces rehabilitation period and eliminates functional disorders.

Loss of Smad4 in the scleraxis cell lineage results in postnatal joint contracture.

Growth of the musculoskeletal system requires precise coordination between bone, muscle, and tendon during development. Insufficient elongation of the muscle-tendon unit relative to bone growth results in joint contracture, a condition characterized by reduction or complete loss of joint range of motion. Here we establish a novel murine model of joint contracture by targeting Smad4 for deletion in the tendon cell lineage using Scleraxis-Cre (ScxCre). Smad4ScxCre mutants develop a joint contracture shortly after birth. The contracture is stochastic in direction and increases in severity with age. Smad4ScxCre mutant tendons exhibited a stable reduction in cellularity and a progressive reduction in extracellular matrix volume. Collagen fibril diameters were reduced in the Smad4ScxCre mutants, suggesting a role for Smad4 signaling in the regulation of matrix accumulation. Although ScxCre also has sporadic activity in both cartilage and muscle, we demonstrate an essential role for Smad4 loss in tendons for the development of joint contractures. Disrupting the canonical TGFß-pathway in Smad2;3ScxCre mutants did not result in joint contractures. Conversely, disrupting the BMP pathway by targeting BMP receptors (Alk3ScxCre/Alk6null) recapitulated many features of the Smad4ScxCre contracture phenotype, suggesting that joint contracture in Smad4ScxCre mutants is caused by disruption of BMP signaling. Overall, these results establish a model of murine postnatal joint contracture and a role for BMP signaling in tendon elongation and extracellular matrix accumulation.

The Genomics of Arthrogryposis, a Complex Trait: Candidate Genes and Further Evidence for Oligogenic Inheritance.

Arthrogryposis is a clinical finding that is present either as a feature of a neuromuscular condition or as part of a systemic disease in over 400 Mendelian conditions. The underlying molecular etiology remains largely unknown because of genetic and phenotypic heterogeneity. We applied exome sequencing (ES) in a cohort of 89 families with the clinical sign of arthrogryposis. Additional molecular techniques including array comparative genomic hybridization (aCGH) and Droplet Digital PCR (ddPCR) were performed on individuals who were found to have pathogenic copy number variants (CNVs) and mosaicism, respectively. A molecular diagnosis was established in 65.2% (58/89) of families. Eleven out of 58 families (19.0%) showed evidence for potential involvement of pathogenic variation at more than one locus, probably driven by absence of heterozygosity (AOH) burden due to identity-by-descent (IBD). RYR3, MYOM2, ERGIC1, SPTBN4, and ABCA7 represent genes, identified in two or more families, for which mutations are probably causative for arthrogryposis. We also provide evidence for the involvement of CNVs in the etiology of arthrogryposis and for the idea that both mono-allelic and bi-allelic variants in the same gene cause either similar or distinct syndromes. We were able to identify the molecular etiology in nine out of 20 families who underwent reanalysis. In summary, our data from family-based ES further delineate the molecular etiology of arthrogryposis, yielded several candidate disease-associated genes, and provide evidence for mutational burden in a biological pathway or network. Our study also highlights the importance of reanalysis of individuals with unsolved diagnoses in conjunction with sequencing extended family members.

Development of a novel knee contracture mouse model by immobilization using external fixation.

AIMS: Several studies have used animal models to examine knee joint contracture; however, few reports detail the construction process of a knee joint contracture model in a mouse. The use of mouse models is beneficial, as genetically modified mice can be used to investigate the pathogenesis of joint contracture. Compared to others, mouse models are associated with a lower cost to evaluate therapeutic effects. Here, we describe a novel knee contracture mouse model by immobilization using external fixation. METHODS: The knee joints of mice were immobilized by external fixation using a splint and tape. The passive extension range of motion (ROM), histological and immunohistochemical changes, and expression levels of fibrosis-related genes at 2 and 4 weeks were compared between the immobilized (Im group) and non-immobilized (Non-Im group) groups. RESULTS: The extension ROM at 4 weeks was significantly lower in the Im group than in the Non-Im group (p < 0.01). At 2 and 4 weeks, the thickness and area of the joint capsule were significantly greater in the Im group than in the Non-Im group (p < 0.01 in all cases). At 2 weeks, the mRNA expression levels of the fibrosis-related genes, except for the transforming growth factor-ß1, and the protein levels of cellular communication network factor 2 and vimentin in the joint capsule were significantly higher in the Im group (p < 0.01 in all cases). CONCLUSION: This mouse model may serve as a useful tool to investigate the etiology of joint contracture and establish new treatment methods.

Adipose stem cells exhibit mechanical memory and reduce fibrotic contracture in a rat elbow injury model.

Fibrosis is driven by a misdirected cell response causing the overproduction of extracellular matrix and tissue dysfunction. Numerous pharmacological strategies have attempted to prevent fibrosis but have attained limited efficacy with some detrimental side effects. While stem cell treatments have provided more encouraging results, they have exhibited high variability and have not always improved tissue function. To enhance stem cell efficacy, we evaluated whether mechanical memory could direct cell response. We hypothesized that mechanically pre-conditioning on a soft matrix (soft priming) will delay adipose-derived stem cell (ASC) transition to a pro-fibrotic phenotype, expanding their regenerative potential, and improving healing in a complex tissue environment. Primary ASCs isolated from rat and human subcutaneous fat exhibited mechanical memory, demonstrated by a delayed cell response to stiffness following two weeks of soft priming including decreased cell area, actin coherency, and extracellular matrix production compared to cells on stiff substrates. Soft primed ASCs injected into our rat model of post-traumatic elbow contracture decreased histological evidence of anterior capsule fibrosis and increased elbow range-of-motion when evaluated by joint mechanics. These findings suggest that exploiting mechanical memory by strategically controlling the culture environment during cell expansion may improve the efficacy of stem cell-based therapies targeting fibrosis.

A rat model of arthrofibrosis developed after anterior cruciate ligament reconstruction without rigid joint immobilization.

Purpose: Complications including arthrofibrosis have been reported after anterior cruciate ligament reconstruction (ACLR) even under accelerated rehabilitation. To overcome this, we developed an animal model of ACLR-induced arthrofibrosis without immobilization.Materials and Methods: Thirteen male Wistar rats were divided into ACL transection (ACLT) and ACLR groups. Surgery was performed in the right knees and untreated left knees were used as controls. After surgery, rats could move freely without joint immobilization.Results: One week after surgery, flexion contracture represented by passive ROM reduction was 49 ± 5° and 21 ± 6° in ACLR and ACLT groups, respectively. Thereafter, flexion contractures were gradually reduced to 21 ± 8° and 12 ± 6° after 12 weeks, respectively. Fibrosis, which is characterized by significant upregulation of fibrosis-related genes, thickening, and adhesion in the posterior joint capsule, was observed in the ACLR group after 12 weeks of surgery. Nociceptive behavior and joint swelling were more apparent in the ACLR group than in the ACLT group, especially after 1 week of surgery.Discussions: We developed a rat model of ACLR-induced joint contracture due to arthrofibrosis without rigid immobilization. Joint contracture was also observed in the ACLT group, but to a considerably milder degree than in the ACLR group. Thus, signs of inflammation as a result of reconstruction surgery, rather than ACL transection, play an important role in the formation of joint contracture after ACLR. Our animal model is suited to examine the mechanisms and efficacy of therapeutic strategies for arthrofibrosis following ACLR treated without rigid joint immobilization.

Effectiveness of Flexor Tenotomy With a Transpositional Skin Flap for the Treatment of Severe Claw Toe Deformity With Mild-to-Moderate Joint Contracture.

Flexor tenotomy is the most effective for achieving healing and for the prevention of toe ulcer resulting from claw toe deformity. Although flexor tenotomy might be effective for a flexible claw toe, it might not provide benefits for severe claw toe deformity involving joint contracture. We devised a method involving the transfer of a flap to the skin defect caused by tenotomy, as severe claw toe deformity is associated with skin contracture. Although transpositional skin flap might increase the postoperative complication risks, it can be effectively used for severe claw toe deformity involving mild-to-moderate joint contracture.

Linear Morphea With Inflammatory Myositis.

Morphea is an autoimmune disorder characterized by sclerosis and inflammation of the skin and soft tissues. Early diagnosis and treatment are essential to minimize morbidity such as joint contracture. In this report, we present the case of a 19-year-old man with linear morphea with inflammatory myositis who presented to our clinic 1 year after symptom onset with severe elbow flexion contracture. Through reviewing this rare disorder, it is hoped that early diagnosis will lead to better outcomes in the future.

Open Reduction of Neglected Dislocations of the Proximal Interphalangeal Joint.

Chronic unreduced dislocations of the proximal interphalangeal joint are uncommon and management principles for these injuries have not been defined. The dislocation can be volar or dorsal and closed reduction is rarely successful owing to soft tissue contractures. We describe an extensile midaxial approach to the proximal interphalangeal joint for release of contractures, open reduction, and repair of critical structures. A smaller contralateral incision can be made if needed for additional soft tissue release. Using illustrative cases, we discuss technical points that are essential for a successful outcome and common pitfalls that could lead to complications. A functional range of motion with a stable joint can be achieved as long as articular cartilage is relatively preserved.

Contracture and transient receptor potential channel upregulation in the anterior glenohumeral joint capsule of patients with end-stage osteoarthritis.

BACKGROUND: During anatomic total shoulder arthroplasty (TSA) for primary glenohumeral osteoarthritis (GHOA), the anterior shoulder joint capsule (ASJC) is characterized grossly by contracture, synovitis, and fibrosis. In tissues that develop fibrosis, there is substantial cross-talk between macrophages, fibroblasts, and myofibroblasts, modulated by calcium signaling and transient receptor potential (TRP) channel signaling. The purpose of this study was to compare and characterize the degree of synovitis, inflammatory infiltrate, and TRP channel expression in ASJC harvested from shoulders with and without primary GHOA. METHODS: The ASJC was resected from patients undergoing TSA for primary GHOA or other diagnoses and compared with ASJC from cadaveric donors with no history of shoulder pathology. ASJC was evaluated by immunohistochemistry to characterize synovial lining and capsular inflammatory cell infiltrate and fibrosis, and to evaluate for expression of TRPA1, TRPV1, and TRPV4, known to be involved in fibrosis in other tissues. Blinded sections were evaluated by 3 graders using a semiquantitative scale; then results were compared between diagnosis groups using nonparametric methods. RESULTS: Compared with normal control, the ASJC in primary GHOA had significantly increased synovitis, fibrosis, mixed inflammatory cell infiltrate including multiple macrophages subsets, and upregulation of TRP channel expression. CONCLUSION: These data support the clinical findings of ASJC and synovial fibrosis in primary GHOA, identify a mixed inflammatory response, and identify dysregulation of TRP channels in the synovium and joint capsule. Further studies will identify the role of synovial and capsular fibrosis early in the development of GHOA.

[The Therapeutic Effect and Mechanism of Static Progressive Stretching in Different Durations on Traumatic Knee Contracture in Rats].

OBJECTIVE: To investigate the effect and mechanism of static progressive stretching (SPS) in different durations on traumatic knee contracture in rats. METHODS: Seventy male Wistar rats were randomly divided into three groups, including surgical modeling group ( n=50), control group (CON, no surgery, no treatment, n=10) and trauma without immobilization group (TRA, no treatment, n=10). The knee contracture model was established, and 50 surgical modeling rats were randomly divided into five groups including static progressive stretching treatment for 20 minutes group (S20 min, n=10), treatment for 30 minutes group (S30 min, n=10), treatment for 40 minutes group (S40 min, n=10), untreatment group (UNT, no SPS, n=10) and modeling group (MOD, n=10, euthanized after immobilization for histological staining and Western blot). Individuals in the S20 min, S30 min, and S40 min groups were anesthetized and submitted to SPS. One treatment session took place every other day. A total of 8 sessions were given till the final treatment session on the day 16. On the day 0, 8, and 16 of intervention, the range of joint motion (ROM) and gait analysis were measured and compared. After the ROM measurements and gait analysis, the rats were euthanized on the day 16 and the samples were stained with HE and Masson methods. The changes of pathological organization were observed. Western blot was used to detect the expressions of transforming growth factor-ß1 (TGF-ß1) and interleukin-6 (IL-6). RESULTS: ① ROM：the ROM of S30 min group recovered similar to that of the S20 min and S40 min groups after 8 days of treatment ( P>0.05), and was the best among all the surgical modeling groups after 16 d of treatment ( P<0.05). The ROM of S20 min, S30 min and S40 min groups significantly improved on the day 8 and day 16 comparing with that on day 0 ( P<0.01). ② Gait analysis: the stands in the S30min group improved best on the day 8 and day 16 ( P<0.05) , and better than that on day 0 ( P<0.05). The stride length of the S30 min group progressed similar to that of the S40 min group on the day 8 ( P>0.05), and there was no difference among three groups on the day 16 ( P>0.05). The stride length of the S30 min group appeared to recover more quickly on the day 8 ( P<0.05), and those of S20 min and UNT groups recovered significantly on the day 16 ( P<0.05). In addition, the swings in the S30 min group improved best ( P<0.05), and it appeared to recover better on the day 16 ( P<0.05). There was no statistical difference in terms of the swing speed among the four surgical modeling groups on the day 8 ( P>0.05). The swing speed of the S30min group increased most than those of the other three groups ( P<0.05), and it was much better on the day 8 and day 16 comparing with that on the day 0 ( P<0.05 ). ③ HE and Masson staining: the fibrosis and inflammation of the S30min group were significantly suppressed comparing to the other groups on the day 16. ④ Western blot: The protein expression levels of TGF-ß1 and IL-6 were significantly lower than those in the other intervention groups including the S20 min, S40 min and UNT groups on the day 16 ( P<0.05). CONCLUSION: Static progressive stretching treatment for 30 min could significantly improve the traumatic knee contracture in rats. The mechanism may be that the SPS decreased the expressions of TGF-ß1 and IL-6, reduced the adhesion and inflammation of joint capsule. Therefore it relieved the pain and increased the joint mobility by reconstructing the structure of the capsule and suppressing the fibrotic changes.

The mechanisms and treatments of muscular pathological changes in immobilization-induced joint contracture: A literature review.

The clinical treatment of joint contracture due to immobilization remains difficult. The pathological changes of muscle tissue caused by immobilization-induced joint contracture include disuse skeletal muscle atrophy and skeletal muscle tissue fibrosis. The proteolytic pathways involved in disuse muscle atrophy include the ubiquitin-proteasome-dependent pathway, caspase system pathway, matrix metalloproteinase pathway, Ca2+-dependent pathway and autophagy-lysosomal pathway. The important biological processes involved in skeletal muscle fibrosis include intermuscular connective tissue thickening caused by transforming growth factor-ß1 and an anaerobic environment within the skeletal muscle leading to the induction of hypoxia-inducible factor-1α. This article reviews the progress made in understanding the pathological processes involved in immobilization-induced muscle contracture and the currently available treatments. Understanding the mechanisms involved in immobilization-induced contracture of muscle tissue should facilitate the development of more effective treatment measures for the different mechanisms in the future.