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.

This study investigated the effects of treadmill walking during remobilization on range of motion (ROM) and histopathology in rat knee joints, which were immobilized for 3 wk in a flexed position. After fixator removal, rats were divided into a no-intervention (RM) group and a group forced to walk on a treadmill daily at 12 m/min for 60 min (WALK group). Passive knee extension ROMs were measured before (m-ROM) and after (a-ROM) knee flexor myotomy on the first and last day of a 7-day remobilization period, with m-ROM mainly reflecting myogenic factors and a-ROM reflecting arthrogenic factors. Knee joints were histologically analyzed and gene expression of inflammatory or fibrosis-related mediators in the posterior joint capsule were examined. m-ROM and a-ROM restrictions were established after immobilization. m-ROM significantly increased following the remobilization period both in RM and WALK groups compared with that of immobilized (IM) group. Conversely, a-ROM decreased following the remobilization period in both RM and WALK groups compared with that of IM group. Importantly, a-ROM was smaller in the WALK group than the RM group. Remobilization without intervention induced inflammatory and fibrotic reactions in the posterior joint capsule after 1 and 7 days. Treadmill walking promoted these reactions and also increased the expression of fibrosis-related TGF-β1 and collagen type I and III genes. While free movement after immobilization improved myogenic contracture, arthrogenic contracture worsened. Treadmill walking further aggravated arthrogenic contracture through amplified inflammatory and fibrotic reactions. Thus active exercise immediately after immobilization may not improve immobilization-induced joint contracture. NEW & NOTEWORTHY In clinical practice, it is widely accepted that facilitation of joint movements is effective in improving immobilization-induced joint contracture. However, whether active exercises improve arthrogenic contracture is not known. In this study, we revealed that treadmill walking further promoted remobilization-induced progression of arthrogenic contracture. To our knowledge, this is the first study demonstrating no favorable effect of active exercise on immobilization-induced arthrogenic contracture.

BackgroundWhole-body vibration has been suggested for the prevention of muscle mass loss and muscle wasting as an attractive measure for disuse atrophy. This study examined the effects of daily intermittent whole-body vibration and weight bearing during hindlimb suspension on capillary number and muscle atrophy in rat skeletal muscles.MethodsSixty male Wistar rats were randomly divided into four groups: control (CONT), hindlimb suspension (HS), HS + weight bearing (WB), and HS + whole-body vibration (VIB) (n = 15 each). Hindlimb suspension was applied for 2 weeks in HS, HS + WB, and HS + VIB groups. During suspension, rats in HS + VIB group were placed daily on a vibrating whole-body vibration platform for 20 min. In HS + WB group, suspension was interrupted for 20 min/day, allowing weight bearing. Untreated rats were used as controls.ResultsSoleus muscle wet weights and muscle fiber cross-sectional areas (CSA) significantly decreased in HS, HS + WB, and HS + VIB groups compared with CONT group. Both muscle weights and CSA were significantly greater in HS + WB and HS + VIB groups compared with HS group. Capillary numbers (represented by capillary-to-muscle fiber ratio) were significantly smaller in all hindlimb suspension-treated groups compared with CONT group. However, a reduction in capillary number by unloading hindlimbs was partially prevented by whole-body vibration. These findings were supported by examining mRNA for angiogenic-related factors. Expression levels of a pro-angiogenic factor, vascular endothelial growth factor-A mRNA, were significantly lower in all hindlimb suspension-treated groups compared with CONT group. There were no differences among hindlimb suspension-treated groups. Expression levels of an anti-angiogenic factor, CD36 (receptor for thrombospondin-1) mRNA, were significantly higher in all hindlimb suspension-treated groups compared with CONT group. Among the hindlimb suspension-treated groups, expression of CD36 mRNA in HS + VIB group tended to be suppressed (less than half the HS group).ConclusionsOur results suggest that weight bearing with or without vibration is effective for disuse-derived disturbance by preventing muscle atrophy, and whole-body vibration exercise has an additional benefit of maintaining microcirculation of skeletal muscle.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2474-15-315) contains supplementary material, which is available to authorized users.

Joint inflammation following remobilization is an important factor in the progression of arthrogenic contracture. We evaluated the effects of an anti-inflammatory treatment during the remobilization period of recovery after joint immobilization in rats. Three groups of rats had their right knee joints immobilized for 3 weeks using an external fixator at a flexion of 140° to generate flexion contracture. Next, the fixation device was removed, allowing immobilized knees to freely move again for 1 or 7 days. These rats were daily injected with either the steroidal anti-inflammatory drug dexamethasone or saline. Untreated knees were used as controls. At 1 day of remobilization, gene expression of pro-inflammatory cytokines, interleukin (IL)-1β, and IL-6 were both increased in the posterior joint capsule, while dexamethasone treatment inhibited increase of these markers. Passive extension range of motion (ROM) was measured before and after myotomy of the knee flexors. Restriction of ROM before myotomy mainly represents the myogenic, and ROM after myotomy shows the arthrogenic changes. Joint immobilization reduced ROM both before and after myotomy. Seven days of remobilization improved ROM before but not after myotomy. Arthrogenic contracture progression following remobilization was characterized by fibrotic reactions of hypercellularity, upregulation of collagen genes, and increased type I and III collagen proteins in the posterior joint capsule. Dexamethasone treatment during the remobilization period improved both myogenic and arthrogenic contractures. Furthermore, remobilization-induced fibrotic reactions in the joint capsule were mostly prevented using dexamethasone. Anti-inflammatory treatment during the recovery period may be a potential therapeutic treatment for joint contracture.

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