Effects of Weight Bearing on Marrow Adipose Tissue and Trabecular Bone after Anterior Cruciate Ligament Reconstruction in the Rat Proximal Tibial Epiphysis.

The effects of mechanical unloading after anterior cruciate ligament (ACL) reconstruction on bone and marrow adipose tissue (MAT) are unclear. We investigated weight bearing effects on bone and MAT after ACL reconstruction. Rats underwent unilateral knee ACL transection and reconstruction, followed by hindlimb unloading (non-weight bearing), no intervention (low-weight bearing, the hindlimb standing time ratio (STR; operated/contralateral) during treadmill locomotion ranging from 0.55 to 0.91), or sustained morphine administration (moderate-weight bearing, STR ranging from 0.80 to 0.95). Untreated rats were used as controls. At 7 or 14 days after surgery, changes in trabecular bone and MAT in the proximal tibial were assessed histologically. Histological assessments at 7 or 14 days after surgery showed that ACL reconstruction without post-operative intervention did not significantly change trabecular bone and MAT areas. Hindlimb unloading after ACL reconstruction induced MAT accumulation with adipocyte hyperplasia and hypertrophy within 14 days, but did not significantly affect trabecular bone area. Increased weight bearing through morphine administration did not affect trabecular bone and MAT parameters. Our results suggest that early weight bearing after ACL reconstruction is important in reducing MAT accumulation, and that reduction in weight bearing alone is not sufficient to induce bone loss early after ACL reconstruction.

The Effects of Corticosteroid Administration and Treadmill Exercise on Marrow Adipose Tissue and Trabecular Bone after Anterior Cruciate Ligament Reconstruction in Rats.

We aimed to investigate the effects of short-term corticosteroid administration after anterior cruciate ligament (ACL) reconstruction on marrow adipose tissue (MAT) and trabecular bone mass, as well as to examine whether treadmill exercise can mitigate MAT increase and trabecular bone deterioration caused by corticosteroid. ACL-reconstructed rats were divided into groups: no intervention, daily treadmill exercise (60 min/day), administration of the steroidal drug dexamethasone (250 µg/kg on days 0-5, 7, and 9 post-operatively), or dexamethasone administration combined with treadmill exercise. Untreated rats were served as controls. At day 10 or 30 post-operatively, histological assessments were performed in the proximal tibial epiphysis. MAT accumulation and trabecular bone loss were observed after ACL reconstruction. Dexamethasone promoted MAT accumulation at day 10 post-operatively but did not affect the trabecular bone loss. The MAT accumulation caused by dexamethasone reversed within 21 days after discontinuation. Treadmill exercise did not influence the changes in the MAT and trabecular bone areas. Short-term corticosteroid administration after ACL reconstruction promoted MAT accumulation while not affecting trabecular bone area. The MAT accumulation resulting from corticosteroid administration was reversible after discontinuation. Treadmill exercise could not mitigate the accumulation of MAT caused by corticosteroid administration and did not affect trabecular bone area.

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.

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.

Changes in passive stiffness and length of the semitendinosus muscles in rats with arthritis-induced knee flexion contracture.

BACKGROUND: Arthritis-induced joint contracture is caused by arthrogenic and myogenic factors. The arthrogenic factor, localized within the joint, is naturally accepted as the cause of contracture. However, the detailed mechanisms underlying arthritis-induced myogenic contracture are largely unknown. We aimed to elucidate the mechanisms of arthritis-induced myogenic contracture by examining the muscle mechanical properties. METHODS: Knee arthritis was induced in rats by injecting complete Freund's adjuvant into the right knees, while the untreated contralateral knees were used as controls. After one or four weeks of injection, passive stiffness, length, and collagen content of the semitendinosus muscles were assessed, along with passive knee extension range of motion. FINDINGS: After one week of injection, flexion contracture formation was confirmed by a decreased range of motion. Range of motion restriction was partially relieved by myotomy, but still remained even after myotomy, indicating the contribution of both myogenic and arthrogenic factors to contracture formation. After one week of injection, the stiffness of the semitendinosus muscle was significantly higher in the injected side than in the contralateral side. After four weeks of injection, the stiffness of the semitendinosus muscle in the injected side returned to levels comparable to the contralateral side, parallel to partial improvement of flexion contracture. Muscle length and collagen content did not change due to arthritis at both time points. INTERPRETATION: Our results suggest that increased muscle stiffness, rather than muscle shortening, contributes to myogenic contracture detected during the early stage of arthritis. The increased muscle stiffness cannot be explained by excess collagen.

The effects of weight bearing on muscle atrophy early after ACL reconstruction in rats.

We examined the effects of weight bearing after anterior cruciate ligament (ACL) reconstruction on muscle atrophy in rats. Rats were divided into the following groups: untreated control, ACL reconstruction (amount of weight bearing was small), ACL reconstruction plus hindlimb unloading (nonweight bearing), and ACL reconstruction plus morphine administration (amount of weight bearing was large) groups. At 7 or 14 days after surgery, atrophy of the rectus femoris and gastrocnemius was assessed. ACL reconstruction induced muscle atrophy in the rectus femoris and gastrocnemius. Unloading facilitated atrophy in the gastrocnemius but not in the rectus femoris. Morphine administration partially prevented atrophy in the gastrocnemius but not in the rectus femoris. After ACL reconstruction, the gene expression of insulin-like growth factor-1 (IGF-1), which is involved in protein synthesis, was downregulated in the gastrocnemius. Unloading decreased the gene expression of IGF-1 and increased the gene expression of atrogin-1, which is involved in protein breakdown, in the gastrocnemius. Morphine administration attenuated the downregulation of IGF-1. Atrophy of the gastrocnemius was more severe with a decrease in weight bearing, although the effect of weight bearing on rectus femoris atrophy was limited in rats. Early weight bearing is effective for reducing gastrocnemius muscle atrophy after ACL reconstruction.

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

BACKGROUND: Both 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. METHODS: Rats 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. FINDINGS: Range 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. INTERPRETATION: Our 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.

Effects of joint immobilization and treadmill exercise on marrow adipose tissue and trabecular bone after anterior cruciate ligament reconstruction in the rat proximal tibial epiphysis.

Marrow adipose tissue (MAT) adversely affects bone metabolism under certain conditions. Although mechanical stress is an important factor in regulating MAT and bone mass, how stress from different rehabilitation protocols after anterior cruciate ligament (ACL) reconstruction affects trabecular bone and MAT is unclear. We aimed to examine the effects of joint immobilization and treadmill exercise on trabecular bone and MAT after ACL reconstruction. Rats received unilateral knee ACL transection and reconstruction surgery. After surgery, rats were reared without intervention, with joint immobilization, or with treadmill exercise (12 m/min, 60 min/day, six days/week), with untreated rats as controls. At two or four weeks after starting experiments, we examined histological changes in trabecular bone and MAT in the proximal tibial epiphysis. After ACL reconstruction, there were no significant changes in trabecular bone area and MAT area at both time points. Joint immobilization after ACL reconstruction resulted in reduced trabecular bone area and MAT accumulation due to adipocyte hyperplasia and hypertrophy within four weeks. Treadmill exercise after ACL reconstruction did not affect any parameters in trabecular bone and MAT. We detected a moderate negative correlation between trabecular bone area and MAT area. Therefore, MAT accumulation induced by joint immobilization may contribute, at least in part, to reducing trabecular bone area. To minimize trabecular bone loss and MAT accumulation, joint immobilization after ACL reconstruction should be minimized. Exercise after ACL reconstruction did not alter trabecular bone and MAT.

The combined effects of treadmill exercise and steroid administration on anterior cruciate ligament reconstruction-induced joint contracture and muscle atrophy in rats.

Rehabilitation protocols to treat joint contracture and muscle atrophy following anterior cruciate ligament (ACL) reconstruction have not been established. In this study, we examined the combined effects of exercise therapy and steroid administration on joint contracture and muscle atrophy following ACL reconstruction. Rats received ACL transection and reconstructive surgery in one knee. After surgery, they were divided into four groups: no intervention, treadmill exercise (started from day three post-surgery, 12 m/min, 60 min/d, 6 d/week), treatment with the steroidal drug dexamethasone (250 µg/kg on days 0-5, 7, and 9 post-surgery), and dexamethasone treatment plus treadmill exercise. Age-matched untreated rats were used as controls. At day 10 or 30 post-surgery, we assessed ACL-reconstruction-induced joint contracture, joint capsule fibrosis, osteophyte formation, and muscle atrophy of the rectus femoris and gastrocnemius. Treadmill exercise after ACL reconstruction improved several indicators of muscle atrophy in both muscles, but it did not have positive effects on joint contracture. Dexamethasone treatment after ACL reconstruction improved joint contracture and joint capsule fibrosis at both timepoints and partially attenuated osteophyte formation at day 10 post-surgery, but delayed recovery from atrophy of the rectus femoris at day 30 post-surgery. The two treatments combined improved both joint contracture and atrophy of the rectus femoris and gastrocnemius. Exercise therapy combined with steroid administration may therefore be a novel therapeutic strategy for joint contracture and muscle atrophy following ACL reconstruction.

The effects of the amount of weight bearing on articular cartilage early after ACL reconstruction in rats.

PURPOSE: Osteoarthritis that develops after anterior cruciate ligament (ACL) reconstruction is a critical issue. We examined the effects of the amount of weight bearing early after ACL reconstruction on articular cartilage. MATERIALS AND METHODS: Rats were divided into groups according to the treatment received: untreated control, ACL reconstruction (ACLR), ACL reconstruction plus hindlimb unloading (ACLR + HU), and ACL reconstruction plus morphine administration (ACLR + M). ACL reconstruction was performed on the right knee throughout the groups. To assess the amount of weight bearing, one-hindlimb standing time ratio (STR; operated side/contralateral side) during treadmill locomotion was evaluated during the experimental period. At day 7 or 14 post-surgery, cartilage degeneration of the medial tibial plateau was histologically assessed. RESULTS: In the ACLR group, reduction in weight bearing characterized by significantly reduced STR was observed between day 1 and 7. Reduction in weight bearing was partially attenuated by morphine administration. Compared with the control group, the ACLR group exhibited an increased Mankin score that was accompanied by increased cyclooxygenase-2 expression in the anterior region. In the ACLR + HU group, Mankin scores were significantly higher in the middle and posterior regions, and cartilage thickness in these regions was significantly thinner than those in the ACLR group. In the ACLR + M group, although chondrocyte density in the anterior region was increased, all other parameters were not significantly different from those in the ACLR group. CONCLUSIONS: Our results suggest that early weight bearing after ACL reconstruction is important to reduce cartilage degeneration.

Mechanical properties within and beyond the physiological length of the semitendinosus muscle of knee-immobilized rats.

BACKGROUND: The effects of immobilization on passive muscle mechanical properties are inconsistent between studies. Here, we investigated the mechanical properties of immobilized muscle by obtaining length-force curves within and beyond the physiological muscle-tendon length in a knee-contractured rat model. METHODS: Unilateral rat knee joints were immobilized using an external fixator for up to 21 days. Length-passive force relationships in the immobilized and contralateral semitendinosus muscles were determined by tensile testing. FINDINGS: The semitendinosus muscle-tendon length at end physiologic length in vivo was approximately at 5% strain of the slack length. Dynamic, elastic, and viscous force (three aspects of muscle mechanical properties) evoked by instantaneous constant stretch were higher than contralateral side within the physiological muscle-tendon length limit (strains of 5% or 5%-7.5% slack length). When beyond muscle-tendon length corresponding to the maximum knee extension (strains of 7.5% or 10%-20% slack length), there was no difference between the two sides. Dynamic and elastic stiffness were also larger, as estimated by tangent angles of length-force curves, at strains of 5% slack length, and matched contralateral levels at strains of 7.5% slack length on day 21. There were no differences in semitendinosus muscle-tendon lengths overtime. Despite significantly reductions in knee extension range of motion, collagen content only showed slight changes and correlation was hardly detected between collagen and mechanical properties on day 21. INTERPRETATION: Viscoelasticity in immobilized semitendinosus muscle increased within the physiological muscle-tendon length. Collagen content may have little effect on passive force and stiffness.

Effects of Joint Immobilization and Treadmill Exercise on Articular Cartilage After ACL Reconstruction in Rats.

Background: The development of osteoarthritis after anterior cruciate ligament (ACL) reconstruction (ACLR) is an important issue. However, the appropriate rehabilitation protocol to prevent cartilage degeneration due to postoperative osteoarthritis is unclear. Purpose: To examine the effects of joint immobilization and treadmill exercise on articular cartilage after ACLR. Study Design: Controlled laboratory study. Methods: A total of 55 rats received unilateral knee ACL transection and reconstruction surgery using tail tendon autografts. After surgery, rats were reared without intervention, with joint immobilization, or with daily treadmill exercise (12 m/minute, 60 minutes/day, 6 days/week). Treadmill exercise was initiated at 3 or 14 days postoperatively. After 2 weeks of immobilization, the fixation device was removed from some of the immobilized rats, and the knee was allowed to move freely for 2 weeks. Untreated, age-matched rats (n = 8) were used as controls. At 2 or 4 weeks after starting the experiment, cartilage degeneration in the medial tibial plateau was histologically assessed using a modified Mankin score, cartilage thickness, chondrocyte density, and immunohistochemistry for cyclooxygenase-2 (COX-2) in the anterior, middle, and posterior regions. Results: After ACLR, cartilage degeneration in the anterior region characterized by increased Mankin score, accompanied with increased COX-2 expression, was detected. Joint immobilization after ACLR facilitated cartilage degeneration, which is detected by histological changes such as reductions in cartilage thickness, chondrocyte density, and high Mankin scores. Enhanced COX-2 expression in all degenerated cartilage regions was also detected. It was found that 2 weeks of remobilization could not restore cartilage degeneration induced by 2 weeks of immobilization after ACLR. Treadmill exercise after ACLR did not affect most articular cartilage parameters, regardless of the timing of exercise. Conclusion: Our results indicated that (1) immobilization after ACLR accelerates cartilage degeneration, even when applied only for 2 weeks, and (2) mild exercise during early phases after ACLR does not facilitate cartilage degeneration. Clinical Relevance: To reduce cartilage degeneration, periods of joint immobilization after ACLR should be minimized. Mild exercise during the early phases after ACLR will not negatively affect articular cartilage.

Conflicting time-dependent effects of treadmill exercise on joint contracture after anterior cruciate ligament reconstruction in rats.

We examined the time-dependent differences in the effects of treadmill exercise on joint contracture after anterior cruciate ligament (ACL) reconstruction. Rats received ACL reconstructive surgery. After surgery, rats were reared with or without treadmill exercise (60 min/day) starting at 3 days (when inflammatory reactions are active) or 14 days (when inflammatory reactions have subsided) post-surgery. Untreated rats were used as controls. Data were collected at two or four weeks post-surgery. The range of motion (ROM) decreased following surgery at both time points and treadmill exercise during the first two weeks post-surgery further decreased the ROM. Moreover, treadmill exercise during first two weeks post-surgery upregulated the pro-inflammatory cytokine interleukin-1ß gene in the joint capsule and aggravated joint capsule fibrosis. For exercise started at 14 days post-surgery, the ROM recovered to control levels at four weeks post-surgery. In addition, delayed exercise contributed to resolving inflammatory and fibrotic reactions. Treadmill exercise initiated soon after surgery aggravates joint contracture via enhanced inflammatory and fibrotic reactions in the joint capsule. Conversely, exercise initiated after active inflammation has subsided facilitates joint capsule reorganization and increases joint ROM. Therefore, aggressive exercise should be started only after active inflammation is resolved to improve joint contracture following ACL reconstruction.

Marrow adipose tissue accumulation and dysgenesis of the trabecular bone after anterior cruciate ligament transection and reconstruction in the rat proximal tibial epiphysis.

The accumulation of marrow adipose tissue (MAT) is frequently associated with bone loss. Although anterior cruciate ligament (ACL) injury induces bone loss, MAT accumulation after ACL injury has not been evaluated. In addition, no information about changes in MAT after ACL reconstruction is available. In this study, we aimed to examine (1) the effects of ACL transection on the amounts of trabecular bone and MAT present, and (2) whether ACL reconstruction inhibits the changes in the trabecular bone and MAT that are induced by ACL transection. ACL transection alone or with immediate reconstruction was performed on the right knees of rats. Untreated left knees were used as controls. Histomorphological changes in the trabecular bone and MAT in the proximal tibial epiphysis were examined prior to surgery and at one, four, and 12 weeks postsurgery. The trabecular bone area on the untreated side increased in a time-dependent manner. However, after ACL transection, the trabecular bone area did not increase during the experimental period, indicating dysgenesis of the bone (bone loss). Dysgenesis of the trabecular bone after ACL transection was attenuated by ACL reconstruction. MAT accumulation due to adipocyte hyperplasia and hypertrophy had been induced by ACL transection by four weeks postsurgery. This ACL transection-induced MAT accumulation was not prevented by ACL reconstruction. Based on these results, we conclude that (1) dysgenesis of the bone in the proximal tibia following ACL transection is accompanied by MAT accumulation, and (2) ACL reconstruction attenuates dysgenesis of the trabecular bone but cannot prevent MAT accumulation.

Bilateral muscle atrophy after anterior cruciate ligament reconstruction in rats: Protective effects of anti-inflammatory drug celecoxib.

BACKGROUND: Muscle atrophy after anterior cruciate ligament (ACL) reconstruction occurs bilaterally and contributes to a decrease in muscle strength. However, effective treatment strategies for ACL reconstruction-induced muscle atrophy have not been established. We examined the effects of anti-inflammatory drug on muscle atrophy after ACL reconstruction. MATERIALS AND METHODS: Rats were divided into groups according to treatment received: untreated control (n = 4), arthrotomy (n = 6), ACL transection (n = 7), ACL reconstruction (n = 8), and ACL reconstruction plus anti-inflammatory drug celecoxib (CBX; 50 mg/kg/day) administration (n = 8). At one-week post-surgery, the muscle fiber cross-sectional area (CSA) in the rectus femoris (RF) and semitendinosus (ST) was measured to assess muscle atrophy. In addition, we examined joint swelling and serum C­reactive protein (CRP) levels to assess local and systemic inflammation, respectively. RESULTS: Each additional procedure (i.e., arthrotomy, ACL transection, and ACL reconstruction) gradually decreased the muscle fiber CSAs in the RF and ST on both operated and contralateral sides. The degree of muscle fiber atrophy on the operated side was larger than that detected on the contralateral side. Moreover, ACL reconstruction induced joint swelling on the operated side and tended to increase serum CRP levels. CBX lessened the RF atrophy on both sides and was associated with less joint swelling and a smaller increase CRP level; however, it did not affect ST atrophy on either side. CONCLUSIONS: Anti-inflammatory treatments after ACL reconstruction may be effective in lessening muscle atrophy in the quadriceps, but not in the hamstrings.

Interactive effects of exercise and sleep on frailty severity in community-dwelling older adults: a cross-sectional study.

Objectives: This study examined the effects of the interaction between exercise and sleep on frailty severity in community-dwelling older adults. Materials and Methods: This was a cross-sectional study. Data were collected in July 2019. In total, 2021 adults participated who responded to a questionnaire. Among them, 672 participants (317 men and 355 women) with valid responses were included in the analysis. Ordinal logistic regression analysis was performed to examine the association between frailty severity and the interaction between exercise and sleep. The dependent variable represents three different levels of frailty. The independent variables included basic information and interaction between exercise and sleep. Results: The results of ordinal logistic regression analysis (odds ratio [OR]) showed that the period from the start of exercise (OR=0.96), age (OR=1.00 for participants in their 60 s, OR=1.65 for those in their 70s, and OR=3.13 for those aged >80 years), poor subjective health perception (OR=2.12), poor quality of sleep (OR=1.88), stress (OR=1.62), and exercise-sleep interaction (OR=1.00 based on good-exercise-good-sleep interaction, OR=3.09 poor-exercise-good-sleep interaction, and OR=3.50 poor-exercise-poor-sleep interaction) significantly contributed to the model. The Nagelkerke coefficient of determination adjusted for degrees-of-freedom (R2), which represents the contribution rate of the regression equation, was 0.334. Conclusions: Our results suggest that a combination of good exercise and good sleep is needed to prevent frailty progression in community-dwelling older adults.

Effects of Each Phase of Anterior Cruciate Ligament Reconstruction Surgery on Joint Contracture in Rats.

BACKGROUND: Although anterior cruciate ligament reconstruction surgery is known to cause joint contracture, the mechanisms of this process are unknown. We aimed to assess the effects of transection of this ligament and each phase of reconstruction surgery on contracture formation. MATERIALS AND METHODS: Rats were divided into groups according to treatment received: sham (arthrotomy), ligament transection, ligament transection plus bone drilling, and ligament reconstruction. Surgery was performed on the right knee. Untreated left knees in the sham group were used as controls. RESULTS: At 7 and 28 d post-surgery, range of motion before myotomy, mainly representing myogenic contracture, was restricted in the sham and ligament transection groups, and more so in the bone drilling and reconstruction groups. Restricted range of motion after myotomy, representing arthrogenic contracture, was detected at both timepoints in the bone drilling and reconstruction groups, but not in the sham or ligament transection groups. At 3 d post-surgery, although a large blood clot was observed in all three treatment groups, only the bone drilling and reconstruction groups showed significant joint swelling. At 7 d post-surgery, inflammatory-cell infiltration into the joint capsule was most apparent in the bone drilling and reconstruction groups, and joint capsule fibrosis was also most apparent in these groups at 7 and 28 d post-surgery. CONCLUSIONS: Our results suggest that (1) myogenic contracture after anterior cruciate ligament reconstruction is caused by arthrotomy and aggravated by bone drilling, and (2) arthrogenic contracture is mostly due to bone drilling, which triggers an inflammation-fibrosis cascade.

A rat model of hip joint contracture induced by mono-articular hip joint immobilization.

BACKGROUND: To elucidate the formation process and therapeutic targets of hip flexion contracture, we developed a rat model of hip flexion contracture induced by hip mono-articular immobilization. METHODS: Kirschner wires inserted into the femur and hip bone were anchored at the hip in a flexed position in the immobilization groups and unanchored in the sham groups for up to four weeks. Age-matched untreated rats were used as controls. Hip extension range of motion (RoM) was measured at three different extension moments (7.5, 15, and 22.5 N•mm) in each successive myotomy step as follows: before myotomy, after sequential myotomy of the tensor fascia lata, quadriceps muscle, iliopsoas muscle, and after myotomy of all residual muscles (the gluteus medius and adductor muscles). Histological analysis of the hip joint was also performed. FINDINGS: After four weeks of immobilization, the RoM before myotomy at 22.5 N•mm was significantly decreased by 29° compared with controls, and this value was unaltered in the sham group. Analyses following serial myotomy suggested that the structures responsible for myogenic contracture were the tensor fascia lata, iliopsoas, gluteus medius, and adductor muscles because the RoMs were increased by these myotomies. Unexpectedly, arthrogenic contracture was not detected at moments other than at 7.5 N•mm, even after four weeks of immobilization. Histological analysis confirmed that pathological changes were not apparent in the anterior capsule of the hip joint. INTERPRETATION: The present findings suggest that myogenic contracture may be an important therapeutic target for immobilization-induced hip flexion contracture.

The Natural History of Medial Meniscal Tears in the ACL Deficient and ACL Reconstructed Rat Knee.

OBJECTIVE: The process of anterior cruciate ligament (ACL) injury-induced meniscal tear formation is not fully understood. Clinical studies have shown that ACL reconstruction (ACLR) reduces the development of secondary meniscal tears, but it is difficult to gain insight into the protective effects of ACLR from clinical studies alone. Using rat ACL transection (ACLT) and ACLR models, we aimed to reveal (1) the formation process of meniscal tears secondary to ACLT and (2) the protective effects of ACLR on secondary meniscal tears. DESIGN: ACLT surgery alone or with ACLR was performed on the knees of rats. Histomorphological and histopathological changes were examined in the posteromedial region of the meniscus in intact rats and in rats that received ACLT or ACLR up to 12 weeks postsurgery. In addition, anterior-posterior joint laxity was measured using the universal testing machine to evaluate the effects of ACLT and ACLR on joint laxity. RESULTS: AAnterior-posterior laxity was significantly increased by ACLT compared to the intact knee. This ACLT-induced joint laxity was partially but significantly reduced by ACLR. Meniscal proliferation and hyaline cartilage-like tissue formation were detected in the medial meniscus at 4 weeks post-ACLT. At 12 weeks post-ACLT, hyaline cartilage-like tissue was replaced by ossicles and meniscal tears were observed. These ACLT-induced abnormalities were attenuated by ACLR. CONCLUSIONS: Our results suggest that ACLT-induced joint laxity induces secondary medial meniscal tears through meniscal proliferation and ossicle formation via endochondral ossification. Joint re-stabilization by ACLR suppresses meniscal proliferation and ossicle formation and consequently prevents secondary meniscal tears.

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.