Cory Kim1, Brian Johnstone Ph.D.2
PNWMSRJ. Published online April 15th, 2021.Introduction:
Osteoarthritis (OA) is a highly prevalent disease characterized by the degeneration of joint articular cartilage. It is by far the most common form of arthritis. Obesity has been linked with an increased risk for OA. It was previously thought that this is due to the increased mechanical loading on joints that accelerate the wear and tear of the cartilage. However, Collins et al. have recently shown otherwise. They have shed light on how adipose tissue signaling, through the release of adipokines is a key mediator of joint degeneration. In their study, a mouse model with lipodystrophy (LD), or an absence of fat, was used to directly observe the effects of adipose signaling on OA.
Importance:
This study challenges the long-held dogma that the major influence of adipose tissue on joint degeneration is through the burden of excess weight on the joint tissues. The researchers did so by utilizing transgenic LD mice that cannot store fat. This allowed for the direct measurement of the influences that both adipose tissue and a high fat diet can have on OA. Discovering that paracrine signaling from fat tissue plays a major role in the progression of OA opens up potential avenues of research in the development of therapeutic targets for this joint disease.
Observation:
The study revealed that knee joints from LD mice that were lacking fat were more protected from spontaneous or trauma-induced OA. It was found that LD mice were also protected from OA even when fed a high fat diet, which has otherwise been shown to induce cartilage damage. Furthermore, the researchers implanted adipose tissue from wild type mice into LD mice (WT fat-rescue mice) or injected mouse embryonic fibroblasts from wild type mice (MEF-rescue mice) and found the protective LD effects were reversed; there was a restored susceptibility to OA. These findings indicate that adipose tissue has a significant impact on joint disease independent of its role in increasing body weight.
Conclusions and Relevance:
Previously, it was believed that being overweight or obese caused osteoarthritis due to the increased mechanical forces on joints. This new study has challenged this belief and has shown that there are more complex mechanisms by which adipose tissue influences OA. By use of LD mice, the researchers eliminated weight as a variable and were able to directly study the paracrine influences of adipose tissue on joint degeneration in mice. This research paves the way for new OA therapeutics. Once we know how the signaling influences the progression of the disease, we can then create disease-modifying agents to target these pathways and potentially prevent osteoarthritis, the commonest debilitating joint disease.
References
- Collins KH, Lenz KL, Pollitt EN, et al. Adipose tissue is a critical regulator of osteoarthritis. Proc Natl Acad Sci U S A. 2021;118(1):e2021096118. doi:10.1073/pnas.2021096118
Article information:
Published Online: November 2nd, 2021.
IRB Approval: No IRB approval necessary.
Conflict of Interest Declaration: No conflicts of interest to disclose.
Funding Source/Disclosure: No support provided.