Osteoarthritis (OA) is a disease of the whole joint organ, characterized by the loss of cartilage, and structural changes in bone including the formation of osteophytes, causing disability and loss of function. It is also associated with systemic mediators and low-grade inflammation. Currently, there is negligible/no availability of specific biomarkers that can be used to facilitate the diagnosis and treatment of OA. The most unmet clinical need is, however, related to the monitoring of disease progression over a short period that can be used in clinical trials. In this review, the value of biomarkers identified over the past decade has been highlighted. These biomarkers are associated with the synthesis and breakdown of cartilage, including collagenous and noncollagenous biomarkers, inflammatory and anti-inflammatory biomarkers, expressed in the biological fluid such as serum, synovial fluid, and urine. Broad validation of novel and clinically applicable biomarkers and their involvement in the pathways are particularly needed for early-stage diagnosis, monitoring disease progression, and severity and examining new drugs to mitigate the effects of this highly prevalent and debilitating condition.

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Exploration of the dual and opposing facets of estrogen (E2) necessitate a clear understanding to diminish the controversy of estrogen regulation in averting the systemic, autoimmune, joint degrading disorder, rheumatoid arthritis (RA). Experimental evidences consider estrogen as a pivotal enzyme to modulate the disease progression via managing several cellular mechanisms targeting inflammatory markers such as TNF, ILs, NF-κB and other regulatory proteins like MMPs impeding joint erosion and cartilage degradation. E2 modulates cellular signalling associated with inflammation, oxidative stress, related cardiovascular risk and miRNA regulation during RA progression. Studies determining E2 regulation in RA complicate the resemblance of the outcome as they represent both hyper and hypo level of E2 linked to the disease. Although some reports deliver E2 as malign, there is now increasing evidence of rendering protection dose dependently. Variation in estrogen level cause differential expression of certain proteins and their related signalling which directly or indirectly linked to RA pathogenesis. This review summarizes the variations in protein expression levels by focusing on the in vitro, in vivo and clinical studies of E2 deficiency and treatment. Construction of PPI network, GO and KEGG pathway enrichment analysis of the differentially expressed proteins assist in hypothesizing a potential molecular mechanism of E2 in RA via in silico studies. Targeting these differential proteins can emerge a new path for developing advanced therapeutic strategies.