Nomura M1,2, Wakimoto Y1, Inoue S1, Yakuwa T1, Li C1, Kinoshita S3, Tsubaki T3, Hatakeyama J3, Wakigawa T3, Moriyama H4
1Kobe University Graduate School of Health Sciences, Department of Rehabilitation Science, Kobe, Japan, 2Research Fellow of Japan Society for the Promotion of Science, Tokyo, Japan, 3Kobe University School of Medicine Faculty of Health Sciences, Physical Therapy Major, Kobe, Japan, 4Kobe University, Life and Medical Sciences Area, Health Sciences Discipline, Kobe, Japan
Background: Articular cartilage and underlying subchondral bone play a pivotal role in the function of the musculoskeletal system by producing smooth articulations and shock-absorbing properties of the joints. Mechanical force generated by weight-bearing is essential for the maintenance of them, as we previously reported that the absence of mechanical load caused by non-weight-bearing led to thinning of articular cartilage and subchondral bone atrophy. Although the degeneration of articular cartilage following skeletal unloading has been shown to be recovered after reloading, reversibility of the subchondral bone atrophy remains unclear. Further, it is unknown whether exercise intervention is effective for the restoration and how the reloaded joint responds to mechanical overloading.
Purpose: The aim of this study was to determine whether joint reloading with or without daily running restores unloading-induced degeneration of articular cartilage and subchondral bone, and to investigate the effect of joint unloading followed by reloading on the development of cartilage destruction secondary to joint instability.
Methods: Twelve 8-week-old male C57BL/6 mice were used in this study. Half of the animals were housed under normal condition, whereas the remaining 6 animals underwent hindlimb unloading by tail suspension for 2 weeks and subsequent reloading. Each 6 animals were then equally divided and subjected to one the following 3 conditions (N = 2 animals per condition): no intervention, forced treadmill running (20% incline, 17 m/sec corresponding to 80% maximum oxygen consumption, 40 min/day, every day), and surgical destabilization of the bilateral knee joints (by transection of the medial meniscotibial ligaments). After 4 weeks, both sides of the knee joints were harvested (N = 4 joints per condition) and histological sections prepared sagittally at the medial condyle were stained with safranin-O and fast green. Morphometric parameters including articular cartilage thickness, chondrocyte density, and epiphyseal bone area density were measured and compared with one-way ANOVA followed by Tukey's post hoc test. Further, we evaluated cartilage destruction in the destabilized knees using the OARSI scoring system and compared the results with Mann-Whitney test.
Results: Cartilage thickness was comparable among the all conditions (P > 0.05). Chondrocyte density was significantly decreased by joint destabilization both after normal housing and hindlimb unloading, compared to all the other conditions (P 0.05). When compared with consistent normal housing, hindlimb unloading followed by reloading with or without exercise intervention and normal housing followed by joint destabilization resulted in subchondral bone plate thickening and significantly increased the bone area density (P 0.05). Cartilage destruction secondary to joint destabilization tended to be more severe at the joints reloaded than those consistently grounded (P = 0.147).
Conclusion(s): Joint reloading with or without running exercise succeeded to restore the cartilage thinning following skeletal unloading but caused subchondral bone thickening, which is a hallmark of osteoarthritis. In addition, cartilage destruction induced by joint instability tended to be more progressive in the joints reloaded after unloading.
Implications: Findings from the current study imply that the joints underwent mechanical unloading and subsequent reloading may be at high risk for the development of osteoarthritis.
Keywords: joint reloading, articular cartilage, subchondral bone
Funding acknowledgements: This work was supported in part by Grant-in-Aid for JSPS Research Fellow Grant Number 18J10874.
Purpose: The aim of this study was to determine whether joint reloading with or without daily running restores unloading-induced degeneration of articular cartilage and subchondral bone, and to investigate the effect of joint unloading followed by reloading on the development of cartilage destruction secondary to joint instability.
Methods: Twelve 8-week-old male C57BL/6 mice were used in this study. Half of the animals were housed under normal condition, whereas the remaining 6 animals underwent hindlimb unloading by tail suspension for 2 weeks and subsequent reloading. Each 6 animals were then equally divided and subjected to one the following 3 conditions (N = 2 animals per condition): no intervention, forced treadmill running (20% incline, 17 m/sec corresponding to 80% maximum oxygen consumption, 40 min/day, every day), and surgical destabilization of the bilateral knee joints (by transection of the medial meniscotibial ligaments). After 4 weeks, both sides of the knee joints were harvested (N = 4 joints per condition) and histological sections prepared sagittally at the medial condyle were stained with safranin-O and fast green. Morphometric parameters including articular cartilage thickness, chondrocyte density, and epiphyseal bone area density were measured and compared with one-way ANOVA followed by Tukey's post hoc test. Further, we evaluated cartilage destruction in the destabilized knees using the OARSI scoring system and compared the results with Mann-Whitney test.
Results: Cartilage thickness was comparable among the all conditions (P > 0.05). Chondrocyte density was significantly decreased by joint destabilization both after normal housing and hindlimb unloading, compared to all the other conditions (P 0.05). When compared with consistent normal housing, hindlimb unloading followed by reloading with or without exercise intervention and normal housing followed by joint destabilization resulted in subchondral bone plate thickening and significantly increased the bone area density (P 0.05). Cartilage destruction secondary to joint destabilization tended to be more severe at the joints reloaded than those consistently grounded (P = 0.147).
Conclusion(s): Joint reloading with or without running exercise succeeded to restore the cartilage thinning following skeletal unloading but caused subchondral bone thickening, which is a hallmark of osteoarthritis. In addition, cartilage destruction induced by joint instability tended to be more progressive in the joints reloaded after unloading.
Implications: Findings from the current study imply that the joints underwent mechanical unloading and subsequent reloading may be at high risk for the development of osteoarthritis.
Keywords: joint reloading, articular cartilage, subchondral bone
Funding acknowledgements: This work was supported in part by Grant-in-Aid for JSPS Research Fellow Grant Number 18J10874.
Topic: Musculoskeletal; Musculoskeletal: lower limb; Disability & rehabilitation
Ethics approval required: Yes
Institution: Kobe University
Ethics committee: Institutional Animal Care and Use Committee
Ethics number: P180606
All authors, affiliations and abstracts have been published as submitted.
