Joint Contracture Formation Research Articles

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

ABSTRACT 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.

Poster 120: Understanding the Biological Basis of Contracture Using a Mouse Model of Single Hindlimb Immobilization-Induced Fibrosis

Poster 120: Understanding the Biological Basis of Contracture Using a Mouse Model of Single Hindlimb Immobilization-Induced Fibrosis

The effects of immobilization duration on joint contracture formation after anterior cruciate ligament reconstruction in rats

BackgroundBoth myogenic and arthrogenic factors contribute to contracture formation after anterior cruciate ligament reconstruction surgery. However, effects of immobilization duration on myogenic and arthrogenic contractures after surgery are unknown. We examined the effects of immobilization duration on contracture formation. MethodsRats were divided into groups according to treatment received: untreated control, knee immobilization, anterior cruciate ligament reconstruction, and anterior cruciate ligament reconstruction plus immobilization. Extension range of motion before and after myotomy as well as histomorphological knee changes were assessed two or four weeks after experiment commencement. Range of motion before myotomy mainly represents contractures due to myogenic factors. Range of motion after myotomy represents arthrogenic factors. FindingsRange of motion before and after myotomy was decreased in the immobilization, reconstruction, and reconstruction plus immobilization groups at both timepoints. In the reconstruction plus immobilization group, range of motion before and after myotomy was significantly smaller than in the immobilization and reconstruction groups. Shortening and thickening of the posterior joint capsule was induced in the immobilization and reconstruction groups. In the reconstruction plus immobilization group, capsule shortening was facilitated via adhesion formation, as compared to the immobilization and reconstruction groups. InterpretationOur results indicate that immobilization after anterior cruciate ligament reconstruction surgery facilitates contracture formation via exacerbation of both myogenic and arthrogenic contractures within two weeks. Capsule shortening would be one of the main mechanisms for severe arthrogenic contracture observed in the reconstruction plus immobilization group. Periods of joint immobilization after surgery should be minimized to reduce contracture.

Metformin reduces myogenic contracture and myofibrosis induced by rat knee joint immobilization via AMPK-mediated inhibition of TGF-β1/Smad signaling pathway

ABSTRACT Purpose The two structural components contributing to joint contracture formation are myogenic and arthrogenic contracture, and myofibrosis is an important part of myogenic contracture. Myofibrosis is a response to long-time immobilization and is described as a condition with excessive deposition of endomysial and perimysial connective tissue components in skeletal muscle. The purpose of this study was to confirm whether metformin can attenuate the formation of myogenic contracture and myofibrosis through the phosphorylation level of adenosine monophosphate-activated protein kinase (AMPK) and inhabitation of subsequent transforming growth factor beta (TGF-β) 1/Smad signaling pathway. Materials and Methods An immobilized rat model was used to determine whether metformin could inhibit myogenic contracture and myofibrosis. The contents of myogenic contracture of knee joint was calculated by measuring instrument of range of motion (ROM), and myofibrosis of rectus femoris were determined by ultrasound shear wave elastography and Masson staining. Protein expression of AMPK and subsequent TGF-β1/Smad signaling pathway were determined by western blot. Subsequently, Compound C, a specific AMPK inhibitor, was used to further clarify the role of the AMPK-mediated inhibition of TGF-β1/Smad signaling pathway. Results We revealed that the levels of myogenic contracture and myofibrosis were gradually increased during immobilization, and overexpression of TGF-β1-induced formation of myofibrosis by activating Smad2/3 phosphorylation. Activation of AMPK by metformin suppressed overexpression of TGF-β1 and TGF-β1-induced Smad2/3 phosphorylation, further reducing myogenic contracture and myofibrosis during immobilization. In contrast, inhibition of AMPK by Compound C partially counteracted the inhibitory effect of TGF-β1/Smad signaling pathway by metformin. Conclusion Notably, we first illustrated the therapeutic effect of metformin through AMPK-mediated inhibition of TGF-β1/Smad signaling pathway in myofibrosis, which may provide a new therapeutic strategy for myogenic contracture.

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

ABSTRACT 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.

Histological characteristic of destructive changes in the shoulder joint at arthrosis model

Late treatment of shoulder joint arthrosis and insufficient assessment of pathogenetic components in the appearance and progression of pathological changes in the cartilage leadto the rapid progression of the disease. Traumatic damage of the joint capsule-ligamentous apparatus and impaired mobility are considered one of the main factors for the developmentof this pathology. But the disturbance of the shoulder joint biomechanicsas a factor in the development of arthrosis remains not fully understood. Objective: to study the dynamics of structural changes in the articular surface of the humerus head in the guinea pigs model, when we reproduced the disturbance of biomechanics and the formation of shoulder joint contracture. Methods: the experiments were carried out on guinea pigsweighing 380–420 g, 5 months old. Reproduced model of surgical limitation of joint mobility, which caused the formation of contracture. Histology and scanning electron microscopy examined the condition of the articular cartilage and subchondral bone after 30, 60 and 90 days after modeling. Results: 30 days after surgery in the articular cartilage, degenerative changes were detected, which progressed with the formation of a joint contracture by the 90th day of observation. Destructive changes in articular cartilage after 60 days were manifested by the destruction of its superficial zone, disturbances in the structure of the matrix and chondrocytes, which led to sclerosis of the subchondral layer after 60 and 90 days. The obtained data confirmed the hypothesis that impaired biomechanics and abnormalloads are an independent factor in the development of arthrosis of the shoulder joint. The most critical period was from 30 up to 60 days. Conclusions: the first 30 days after the disturbance of the biomechanics of the shoulder joint can be considered as a therapeutic window for the medical and functional correction of the pathological process.

Arthrofibrosis and large joint scarring

ABSTRACTLarge joint arthrofibrosis and scarring, involving the shoulder, elbow, hip, and knee, can result in the loss of function and immobility. The pathway of joint contracture formation is still being elucidated and is due to aberrations in collagen synthesis and misorientation of collagen fibrils. Novel antibodies are being developed to prevent arthrofibrosis, and current treatment methods for arthrofibrosis include medical, physical, and surgical treatments. This article describes the biology of joint contracture formation, along with current and future pharmacologic, biologic, and medical interventions.

Accumulation of advanced-glycation end products (AGEs) accelerates arthrogenic joint contracture in immobilized rat knee.

Joint mobility decreases in the elderly and in diabetics, this process is thought to be caused by accumulation of advanced-glycation end products (AGEs). Here, we aimed to elucidate the role of AGEs in joint contracture formation in rat knees. Rats were injected with ribose or saline into the knees twice weekly for 8 weeks. Pentosidine (AGE) levels were measured in the knee-joint tissues. After serial injections, rats were subjected to unilateral knee-joint immobilization in a flexion position for various periods. At day 21, the passive knee ranges of motions (ROMs) were measured. Knee joint histopathology were assessed, and the expression of fibrotic genes in the posterior joint capsules was examined using real-time PCR. Ribose injection induced a 7.0-fold increase in pentosidine levels relative to saline injection. Joint immobilization resulted in equal myogenic ROM restriction in both groups. Arthrogenic ROM restriction was greater with ribose injection in the immobilized joints (p < 0.05), but was not affected in nonimmobilized joints. Type-I (COL1A1) and type-III (COL3A1) collagen gene expression increased significantly in immobilized joints relative to nonimmobilized joints in the ribose group, but was not affected in the saline group. Ribose injection increased COL1A1 expression slightly and COL3A1 expression significantly in immobilized joints. Histologically, inflammatory changes appeared at day 3 of immobilization and peaked at day 7. These responses trended to be more severe and prolonged in the ribose group than in the saline group. Our data provide evidence for a causal relationship between AGEs and joint contracture formation following immobilization. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:854-863, 2018.

Nociception contributes to the formation of myogenic contracture in the early phase of adjuvant-induced arthritis in a rat knee

It is unknown how joint contracture is generated in inflamed joints. This study aimed to clarify the role of nociception on the formation of joint contracture secondary to arthritis. Monoarthritis was induced by intra-articular injections of complete Freund's adjuvant (CFA) into rat knees. On day 5 after CFA injection, the passive extension range of motion (ROM) of knee joints were measured, both before and after myotomy of knee flexors, to evaluate the extent of muscular contribution to CFA-induced joint contracture. The steroidal anti-inflammatory drug dexamethasone could prevent ROM restrictions completely, both before and after myotomy. On the other hand, the opioid analgesic drug morphine did not prevent the development of restricted ROM observed after myotomy, while it did before myotomy. This indicates that nociception contributes to joint contracture through alterations in muscular structure (myogenic factors). Next, we tested the hypothesis that nociception-induced reflexive flexor muscle contractions cause myogenic contracture in arthritic joints. To do this, chemical denervation was performed by Botulinum toxin type A (BTX-A) injections into knee flexor muscles, simultaneously with CFA injections into the knee. As expected, BTX-A could alleviate ROM restrictions observed before myotomy. These findings suggest that nociceptive-related muscle contractions play an essential role in the formation of joint contracture. Thus, our study indicates that analgesic management during an early stage of joint arthritis is an essential mean to prevent the formation of joint contracture. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1404-1413, 2017.

Degree of Contracture Related to Residual Muscle Shoulder Strength in Children with Obstetric Brachial Plexus Lesions.

Little is known about the relation between residual muscle strength and joint contracture formation in neuromuscular disorders. This study aimed to investigate the relation between residual muscle strength and shoulder joint contractures in children with sequelae of obstetric brachial plexus lesion (OBPL). In OBPL a shoulder joint contracture is a frequent finding. We hypothesize that residual internal and external rotator strength and their balance are related to the extent of shoulder joint contracture. Clinical assessment was performed in 34 children (mean 10.0 years) with unilateral OBPL and Narakas classes I-III. External and internal rotation strengths were measured with the shoulder in neutral position using a handheld dynamometer. Strength on the affected side was given as percentage of the normal side. Contracture was assessed by passive internal and external rotations in degrees (in 0° abduction). Mallet classification was used for active shoulder function. External and internal rotation strengths on the affected side were approximately 50% of the normal side and on average both equally affected: 56% (SD 18%) respectively 51% (SD 27%); r = 0.600, p = 0.000. Residual strengths were not related to passive internal or external rotation (p > 0.200). Internal rotation strength (r = - 0.425, p <0.05) was related to Narakas class. Mallet score was related to external and internal rotation strengths (r = 0.451 and r = 0.515, respectively; p < 0.01). The intuitive notion that imbalances in residual muscle strength influence contracture formation cannot be confirmed in this study. Our results are of interest for the understanding of contracture formation in OBPL.

Comparison of Muscular and Articular Factors during Joint Contracture Formation in Acute Spinal Cord Injury

Comparison of Muscular and Articular Factors during Joint Contracture Formation in Acute Spinal Cord Injury

Contrasting alterations of apposed and unapposed articular cartilage during joint contracture formation

Trudel G, Himori K, Uhthoff HK. Contrasting alterations of apposed and unapposed articular cartilage during joint contracture formation. Objective To quantify histologic articular cartilage alterations after immobilization, distinguishing between apposed and unapposed sites in an animal model of joint contracture. Design Experimental controlled trial. Setting Laboratory, in vivo study. Animals Adult male Sprague-Dawley rats (N=128). Interventions One hundred seventeen animals had 1 knee internally immobilized or sham-operated for 2, 4, 8, 16, or 32 weeks. One knee in 11 nonoperated animals served as controls. Main outcome measures On standardized sections, we identified femur and tibia cartilage sites that were apposed or that were unapposed. We quantified 4 characteristics: number of chondrocytes in the superficial and deep cartilage; matrix staining intensity to toluidine blue; surface irregularity of articular cartilage; and thickness of cartilage. Results Immobilized knees harbored fewer chondrocytes in the superficial cartilage at apposed sites and in the deep cartilage at unapposed sites. Matrix staining decreased only at unapposed sites. Cartilage surface became significantly more irregular at both sites but cartilage thickness remained unchanged. Noncartilaginous tissues appeared only at unapposed sites in the superficial and deep cartilage. Conclusions Immobilization led to contrasting patterns of cartilage degeneration at apposed sites compared with unapposed sites. These results suggest distinct pathogenetic pathways for cartilage alterations, possibly through absence of mechanical forces (negative mechanotransduction) at unapposed sites and cyclic pressure at apposed sites. Considering the limited potential for cartilage self-repair, these results support the need for early diagnosis and aggressive mobilization of joints that are developing contractures.