Noninflammatory Joint Contractures Arising from Immobility: Animal Models to Future Treatments

Wong, Kayleigh; Trudel, Guy; Laneuville, Odette

doi:10.1155/2015/848290

Cited by 53 publications

(49 citation statements)

References 58 publications

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“…relaxin | fibrosis | frozen shoulder | arthrofibrosis A rthrofibrosis is an accumulation of fibrotic collagenous tissue within the joint, frequently occurring after trauma, surgical procedures, inflammation, prolonged joint immobilization, or idiopathically (1)(2)(3)(4)(5). It manifests as a painful and longstanding restriction of joint range of motion (ROM) (6). Depending on severity and joint location, patients experience limitations in performing even basic activities of daily living, such as ambulation, self-care, and ability to work, thus significantly undermining quality of life for prolonged periods of a year or more (7).…”

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confidence: 99%

Intraarticular injection of relaxin-2 alleviates shoulder arthrofibrosis

Blessing

Okajima

Cubria

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Arthrofibrosis is a prevalent condition affecting greater than 5% of the general population and leads to a painful decrease in joint range of motion (ROM) and loss of independence due to pathologic accumulation of periarticular scar tissue. Current treatment options are limited in effectiveness and do not address the underlying cause of the condition: accumulation of fibrotic collagenous tissue. Herein, the naturally occurring peptide hormone relaxin-2 is administered for the treatment of adhesive capsulitis (frozen shoulder) and to restore glenohumeral ROM in shoulder arthrofibrosis. Recombinant human relaxin-2 down-regulates type I collagen and α smooth muscle actin production and increases intracellular cAMP concentration in human fibroblast-like synoviocytes, consistent with a mechanism of extracellular matrix degradation and remodeling. Pharmacokinetic profiling of a bolus administration into the glenohumeral joint space reveals the brief systemic and intraarticular (IA) half-lives of relaxin-2: 0.96 h and 0.62 h, respectively. Furthermore, using an established, immobilization murine model of shoulder arthrofibrosis, multiple IA injections of human relaxin-2 significantly improve ROM, returning it to baseline measurements collected before limb immobilization. This is in contrast to single IA (sIA) or multiple i.v. (mIV) injections of relaxin-2 with which the ROM remains constrained. The histological hallmarks of contracture (e.g., fibrotic adhesions and reduced joint space) are absent in the animals treated with multiple IA injections of relaxin-2 compared with the untreated control and the sIA-and mIV-treated animals. As these findings show, local delivery of relaxin-2 is an innovative treatment of shoulder arthrofibrosis. relaxin | fibrosis | frozen shoulder | arthrofibrosis

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mentioning

confidence: 99%

Intraarticular injection of relaxin-2 alleviates shoulder arthrofibrosis

Blessing

Okajima

Cubria

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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“…The development of treatments for arthrogenic contracture is thus a necessary step to prevent the irreversible progression of joint contracture. However, joint contractures respond poorly to conventional treatments . For example, passive joint movements, including stretching, are commonly applied clinical treatments against joint contracture.…”

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confidence: 99%

Development of arthrogenic joint contracture as a result of pathological changes in remobilized rat knees

et al. 2017

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This study aimed to elucidate how rats recover from immobilization-induced knee joint contracture. Rats' right knees were immobilized by an external fixator at a flexion of 140° for 3 weeks. After removal of the fixator, the joints were allowed to move freely (remobilization) for 0, 1, 3, 7, or 14 days (n = 5 each). To distinguish myogenic and arthrogenic contractures, the passive extension range of motion was measured before and after myotomy of the knee flexors. Knee joints were histologically analyzed and the expression of genes encoding inflammatory or fibrosis-related mediators, interleukin-1β (1L-1β), fibrosis-related transforming growth factor-β1 (TGF-β1), and collagen type I (COL1A1) and III (COL3A1), were examined in the knee joint posterior capsules using real-time PCR. Both myogenic and arthrogenic contractures were established within 3 weeks of immobilization. During remobilization, the myogenic contracture decreased over time. In contrast, the arthrogenic contracture developed further during the remobilization period. On day 1 of remobilization, inflammatory changes characterized by edema, inflammatory cell infiltration, and upregulation of IL-1β gene started in the knee joint posterior capsule. In addition, collagen deposition accompanied by fibroblast proliferation, with upregulation of TGF-β1, COL1A1, and COL3A1 genes, appeared in the joint capsule between days 7 and 14. These results suggest the progression of arthrogenic contracture following remobilization, which is characterized by fibrosis development, is possibly triggered by inflammation in the joint capsule. It is therefore necessary to focus on developing new treatment strategies for immobilization-induced joint contracture. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1414-1423, 2017.

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“…Joint contracture is characterized by loss of passive range of motion (ROM) and restriction of the activities of daily living, and is an important clinical problem in orthopedics and rehabilitation medicine. The most common cause of joint contracture is immobilization, which is a common orthopedic treatment for patients with severe traumatic injuries of the joints or other musculoskeletal disorders . In addition, several studies demonstrated that patients with conditions limiting their mobility are at a high risk for joint contracture .…”

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confidence: 99%

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

et al. 2017

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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.

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Noninflammatory Joint Contractures Arising from Immobility: Animal Models to Future Treatments

Cited by 53 publications

References 58 publications

Intraarticular injection of relaxin-2 alleviates shoulder arthrofibrosis

Intraarticular injection of relaxin-2 alleviates shoulder arthrofibrosis

Development of arthrogenic joint contracture as a result of pathological changes in remobilized rat knees

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

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