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bioRxiv · 10.1101/2023.03.28.533768

Biochemical reactions between intra-articular tissues and joint instability in a rat model of osteoarthritis

Murata, K.·Kawabata, S.·Kojima, T.·Oka, Y.·Takasu, C.·Terada, H.·Kanemura, N.
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Abstract

AimsJoint instability is associated with various joint conditions including osteoarthritis (OA) and inflammation, and we have developed model which is determined to role of knee instability. Investigating cartilage maintenance factors such as hyaluronic acid (HA) and glycosaminoglycans (GAGs) can provide insights into the effect of the mechanical stress and the inhibitor used, with the following aims: 1) whether cartilage degeneration is inhibited in the new model, 2) whether combination TGF-{beta}1 inhibition mitigates cartilage degeneration, and to determine the role of TGF-{beta}1 in synovitis using fibroblasts. Main methodsWe used this novel model to investigate inhibition of OA progression with a focus on HA and GAGs, which help maintain the cartilage and synovial membrane. In detail, mechanical tests, X-ray, histological, and protein and mRNA expression analyses were used to determine the role of joint stability using in vivo model or fibroblast from synovial membrane. Key findingsJoint stability mitigated cartilage degeneration loss, decreased osteophytes, increased the expression levels of HA and GAGs in the synovial membrane, and decreased the release of pro-inflammatory factors in rats. Moreover, injection of TGF-{beta}1 inhibitor in an inflammatory synovial membrane promoted HA and GAGs expression. In synovial fibroblast cells, inhibition of TGF-{beta}1 over expression significantly inhibited the downregulation of pro-inflammatory factors and promoted the upregulation of lubrification for cartilage. SignificanceOur results suggest that joint instability is an independent mechanical factor for OA progression. The results provide novel insights into the association between OA and joint instability, which has significant human sciences implications. Research Highlights* Established a new experimental rat model of the different joint instability for elucidate osteoarthritis onset/progression * Using Histological staining to investigated the osteoarthritis including synovitis and osteophytes of the novel model * Using fibroblast from synovial membrane to investigated the fibrosis * Joint instability exacerbates articular cartilage degeneration and decreases HA and GAGs protein expressions in synovial membrane * TGF-{beta}1 inhibitor on early osteoarthritis joints may suppress synovial inflammation

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Murata, K., Kawabata, S., Kojima, T., Oka, Y., Takasu, C., Terada, H., Kanemura, N.. 2023-03-29. Biochemical reactions between intra-articular tissues and joint instability in a rat model of osteoarthritis. https://doi.org/10.1101/2023.03.28.533768

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