Less mechanical loading attenuates osteoarthritis by reducing cartilage degeneration, subchondral bone remodelling, secondary inflammation, and activation of NLRP3 inflammasome

Abstract

Aims Osteoarthritis (OA) is a disabling joint disorder and mechanical loading is an important pathogenesis. This study aims to investigate the benefits of less mechanical loading created by intermittent tail suspension for knee OA. Methods A post-traumatic OA model was established in 20 rats (12 weeks old, male). Ten rats were treated with less mechanical loading through intermittent tail suspension, while another ten rats were treated with normal mechanical loading. Cartilage damage was determined by gross appearance, Safranin O/Fast Green staining, and immunohistochemistry examinations. Subchondral bone changes were analyzed by micro-CT and tartrate-resistant acid phosphatase (TRAP) staining, and serum inflammatory cytokines were evaluated by enzyme-linked immunosorbent assay (ELISA). Results Our radiographs showed that joint space was significantly enlarged in rats with less mechanical loading. Moreover, cartilage destruction was attenuated in the less mechanical loading group with lower histological damage scores, and lower expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5, matrix metalloproteinase (MMP)-3, and MMP-13. In addition, subchondral bone abnormal changes were ameliorated in OA rats with less mechanical loading, as reduced bone mineral density (BMD), bone volume/tissue volume (BV/TV), and number of osteophytes and osteoclasts in the subchondral bone were observed. Finally, the level of serum inflammatory cytokines was significantly downregulated in the less mechanical loading group compared with the normal mechanical loading group, as well as the expression of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3), caspase-1, and interleukin 1β (IL-1β) in the cartilage. Conclusion Less mechanical loading alleviates cartilage destruction, subchondral bone changes, and secondary inflammation in OA joints. This study provides fundamental insights into the benefit of non-weight loading rest for patients with OA. Cite this article: Bone Joint Res 2020;9(10):731–741.

Effect of a single intra-articular administration of stanozolol in a naturally occurring canine osteoarthritis model: a randomised trial

“…Also, since stanozolol acts by inducing transforming growth factor 1β synthesis and reducing nitric oxide, it may not significantly impact IL-1 levels. It is also important to keep in mind that exercise influences inflammatory arthropathies parameters, and increase joint loading adds to secondary inflammation in OA joints 48 , 49 . As these animals were working dogs, physical activity may also play a role in this finding.…”

Regulation of TGFβ Signalling by TRPV4 in Chondrocytes

“…There was only a modest enrichment for SP1 and no enrichment for JUN targets following TGFβ3 stimulation without TRPV4 activation, suggesting that TGFβ3 stimulation alone is not enough to activate SP1 and JUN, in this system. It was notable that one of the genes synergistically enhanced by TGFβ3 stimulation and TRPV4 activation is MMP3, which was previously shown to be regulated by JUN [ 52 ] and is responsive to loading in a rat post-traumatic model of OA [ 53 ]. As well as enrichment for TGFβ signalling, our bioinformatic analysis revealed enrichment for focal adhesion pathway genes.…”

Intra-Articular Injection of (−)-Epigallocatechin 3-Gallate (EGCG) Ameliorates Cartilage Degeneration in Guinea Pigs with Spontaneous Osteoarthritis

“…The sections appearing brown or brownish-yellow were considered positive staining. For Col II, the results were assessed with the ratio of the relative density of the brown-stained area to the total area (density/total area) [ 57 , 58 , 59 ]. For MMP-13 and p16 Ink4a , the results were assessed with the immunostaining of positive cells normalized with total cells (positive-stain cell rate) [ 55 , 60 ].…”