Primate skeletal gene regulation: Considering osteoarthritis susceptibility across evolutionary scales

Phenotypic variation within the skeleton has biological, behavioral, and biomedical functional implications for individuals and species. Thus, it is critical to understand how genomic, environmental, and mediating regulatory factors combine and interact to drive skeletal trait development and evolution. One way to do this is by studying skeletal diseases that disrupt skeletal function — like osteoarthritis (OA) which is a chronic disorder characterized by the degradation of cartilage and underlying bone in joints and can lead to severe pain and mobility limitations. Of note, OA susceptibility is not uniformly present throughout the primate order, with high and steadily increasing prevalence rates in humans prompting questions about whether OA is a mismatch disease. However, while OA has a low occurrence in closely related nonhuman apes, many other animals, including other primates, can develop OA just like humans. Disentangling this evolutionary puzzle will require continued efforts to expand skeletal research efforts across species, as well as more targeted investigations of the mechanisms driving OA susceptibility and pathogenesis. Here, I will discuss what is known about OA in humans and other primates, as well as recent advances that are further informing these topics.

Relevant article: Housman G: Advances in skeletal genomics research across tissues and cells. Current Opinion in Genetics & Development 2024, 88:102245.