The degenerative process of osteoarthritis has an enormous impact on athletic longevity of horses and humans. Articular cartilage has a limited capacity for repair from injury in addition to loss of integrity of the cartilage matrix through wear-and-tear over time.
A recent study evaluated therapeutic targets that might improve the low regenerative capacity of cartilage [Martinez-Redondo P., et al. αKLOTHO and sTGFβR2 treatment counteract the osteoarthritic phenotype developed in a rat model. Protein Cell Jan 2020; doi.org/10.1007/s13238-019-00685-7].
The study at the Salk Institute examined two molecules—αKLO-THO and soluble Transforming growth factor-beta receptor 2 (sTGFβR2)—that are involved in homeostasis of human cartilage. The report explains, “The inhibition of the transforming growth factor β isoform 1 (TGFβ1) appears to inhibit osteophyte formation despite increasing proteoglycans degradation, whereas αKLOTHO seems to act as an important inhibitor of extracellular matrix (ECM) degradation.”
Rats were the models for the experimental study, which first induced osteoarthritis via intra-articular injection of papain, which doesn’t affect the chondrocytes. OA was identified four weeks following this injection and compared to the healthy control group. Then αKLO-THO and sTGFβR2 were injected into the rat knees. The study found that the combination of both of these soluble factors resulted in more favorable attenuation of OA than when either was injected alone.
Six weeks following treatment, the rats that received the combination factors had less cartilage deterioration than those without treatment. The treated rats improved from OA Grade 2 to OA Grade 1 within six weeks compared to the untreated rats that progressed to OA Grade 4. Further investigation revealed significant down-regulation of pro-inflammatory cytokines that promote MMP degradation of the extracellular matrix. Besides deterrence of matrix-degrading enzymes, the combination factors also promoted maintenance of cartilage thickness.
This preliminary study holds promise for management of osteoarthritis in both humans and animals. Thus far, use of the combination molecules in vitro on human knee cartilage cells has shown similar favorable effects as the rat model. Additional studies are important to ensure effectiveness and safety in clinical application.