No abstract

Development of OA (OA) is multifactorial and is strongly associated with risk factors such as aging, trauma, metabolic disorders, and obesity. Metabolic Syndrome (MetS)-associated OA, collectively coined MetS-OA, is an increasingly recognized entity in which metabolic disorders and low-grade inflammation play a key mechanistic role in the disruption of joint homeostasis and cartilage degradation. Although there have been enormous efforts to discover biomarkers of MetS and OA, studies investigating a pathophysiological link between MetS and OA are relatively limited, and no serum blood marker has proved diagnostic so far. OA biomarkers that are necessary to discriminate and diagnose early disease remain to be elicited, explained in part by limited prospective studies, and therefore limited tools available to utilize in any prognostic capacity. Biomarker validation projects have been established by the Biomarker Consortium to determine biochemical markers demonstrating predictive validity for knee OA. Given that the metabolic constituents of MetS are treatable to varying extents, it stands to reason that treating these, and monitoring such treatment, may help to mitigate deleterious links with OA development. This narrative review will describe the current state of biomarker identification and utility in OA associated with MetS. We discuss the pathophysiological mechanisms of disease according to constituent pathologies of MetS and how identification of biomarkers may guide future investigation of novel targets.

Osteoarthritis (OA) is a disease of the synovial joint with synovial inflammation, capsular contracture, articular cartilage degradation, subchondral sclerosis and osteophyte formation contributing to pain and disability. Transcriptomic datasets have identified genetic loci in hip and knee OA demonstrating joint specificity. A limited number of studies have directly investigated transcriptional changes in shoulder OA. Further, gene expression patterns of periarticular tissues in OA have not been thoroughly investigated. This prospective case control series details transcriptomic expression of shoulder OA by analysing periarticular tissues in patients undergoing shoulder replacement for OA as correlated with a validated patient reported outcome measure of shoulder function, an increasing (clinically worsening) QuickDASH score. We then compared transcriptomic expression profiles in capsular tissue biopsies from the OA group (N=6) as compared to patients undergoing shoulder stabilisation for recurrent instability (the control group, N=26). Results indicated that top ranked genes associated with increasing QuickDASH score across all tissues involved inflammation and response to stress, namely interleukins, chemokines, complement components, nuclear response factors and immediate early response genes. Some of these genes were upregulated, and some downregulated, suggestive of a state of flux between inflammatory and anti-inflammatory signalling pathways. We have also described gene expression pathways in shoulder OA not previously identified in hip and knee OA, as well as novel genes involved in shoulder OA.