Joint distraction attenuates osteoarthritis by reducing secondary inflammation, cartilage degeneration and subchondral bone aberrant change Y. Chen,

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Joint distraction attenuates osteoarthritis by reducing secondary inflammation, cartilage degeneration and subchondral bone aberrant change Y. Chen, Y. Sun, X. Pan, K. Ho, G. Li Osteoarthritis and Cartilage Volume 23, Issue 10, Pages 1728-1735 (October 2015) DOI: 10.1016/j.joca.2015.05.018 Copyright © 2015 Osteoarthritis Research Society International Terms and Conditions

Fig. 1 The joint distraction device helps enlarging the knee joint space. (a) Custom-made external fixator. The external fixator could be lengthened. (b and c) After frame fixation, passive ROM of flexion and extension were recorded. (d) Animal with the external fixator, the frame was fixed in the medial side of the knee joint. (e) X-ray examination showed that knee joint space was maintained similar as the contralateral knee in the fixation group and the distraction group. The OA group was a negative control. The knee JSW (red arrow) was significantly enlarged in the distraction group compared to the fixation group and the OA group. (f) ELISA assay showed the IL1-β level in serum in the joint distraction group significantly reduced compared to the fixation group and OA group (Dot plot of ELISA result showed mean and 95% CI., n = 5 per group; *P < 0.05: the distraction group compared to the OA group; #P < 0.05: the fixation group compared to the OA group). Osteoarthritis and Cartilage 2015 23, 1728-1735DOI: (10.1016/j.joca.2015.05.018) Copyright © 2015 Osteoarthritis Research Society International Terms and Conditions

Fig. 2 Joint distraction attenuated articular cartilage degeneration in rat OA model. (a) Gross appearance of femoral condyles in the distraction, fixation and OA groups. In the OA group, the medial condyle of the distal femur showed rough joint surface and exhibited osteophyte formation at the intercondylar space; in the distraction group, joint surface of femoral condyles showed relatively smooth and did not find osteophyte formation; and in the fixation group the joint surface of femoral condyles showed some degree of degeneration and small amount of osteophyte formation; (b) Safranin O and fast green staining of sagittal sections of the subchondral tibia medial compartment in the Distraction group, Fixation group and OA group. Scale bar, 800 μm (in top), 200 μm (in bottom). (d) The OARSI scores showed that cartilage degeneration was most sever in the OA group, followed by fixation and joint distraction groups. (c) Immunohistochemical and (e, f) quantitative analysis of the percentages of MMP13+ and type X collagen (COL X)-positive chondrocytes (brown) in articular cartilage showed that joint distraction group significantly reduced the numbers of MMP13+ and type X collagen (COL X)-positive chondrocytes compared to the other two groups. Scale bars, 100 μm n = 5 per group. *P < 0.05: the distraction group compared to the OA group; #P < 0.05: the fixation group compared to the OA group. Osteoarthritis and Cartilage 2015 23, 1728-1735DOI: (10.1016/j.joca.2015.05.018) Copyright © 2015 Osteoarthritis Research Society International Terms and Conditions

Fig. 3 Joint distraction reduced abnormal bone remodeling in subchondral bone in rat OA model. (a) 3D μCT images of the tibia subchondral bone medial compartment (sagittal view) of rats in the distraction group, fixation group and OA group. Scale bar, 1 mm. (b) Quantitative analysis of structural parameters of subchondral bone by μCT analysis. BMD and BV/TV in subchondral bone determined by μCT. n = 5 per group. The results showed that subchondral bone in the OA group had significantly higher BMD and BV/TV in the OA or fixation group comparing to joint distraction group. *P < 0.05: the distraction group compared to the OA group. (c–d) Immunohistochemical analysis and quantification of Nestin and Osterix positive cells (brown) in the tibial subchondral region. Joint distraction group significantly reduced Nestin and Osterix positive cells comparing to the other two groups. Scale bars, 50 μm. *P < 0.05: the distraction group compared to the OA group; #P < 0.05: the fixation group compared to the OA group. Osteoarthritis and Cartilage 2015 23, 1728-1735DOI: (10.1016/j.joca.2015.05.018) Copyright © 2015 Osteoarthritis Research Society International Terms and Conditions