Biomarkers of Joint Damage in Osteoarthritis: Current Status and Future Directions.

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.

Differential Expression of Fibrinogen Alpha and Its Potential Involvement in Osteoarthritis Pathogenesis.

The deterioration of cartilage tissue and other joint components composed of synovial tissue is a defining characteristic of osteoarthritis (OA) disease. Because of the lack of understanding of the underlying cause and important molecular pathways, there are currently no effective diagnostic or treatment methods for OA. The purpose of the study is to find a specific protein biomarker with high sensitivity and specificity in order to understand the pathophysiology of the disease and the underlying molecular pathways. We examined plasma samples of matched age and sex from OA patients (n = 150) and healthy controls (HC) (n = 70) to find proteins that were differentially expressed and validated by western blotting, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, and immunofluorescence. The results of western blotting demonstrated that the expression level of the fibrinogen alpha (FGA) protein was higher in plasma samples of osteoarthritis (OAPL) (p = 0.0343), and the ROC (receiver operating characteristic curve) curve supported the high sensitivity (95.22%) and specificity (74%) of FGA in OA plasma compared to healthy controls. FGA protein was detected to be deposited in the synovial tissue of OA patients (p = 0.0073). By activating the Toll-like receptor (TLR-4) receptor pathway in PBMCs (p = 0.04) and synovial tissue, FGA protein may be involved in the molecular mechanism of OA pathogenesis. Our findings collectively suggested that FGA, which is significantly expressed in OA plasma, synovial tissue, and PBMCs and is connected to the disease's advancement through the TLR-4 receptor, may serve as a diagnostic or disease-evolving tool for OA.

Estrogen-mediated differential protein regulation and signal transduction in rheumatoid arthritis.

Exploration of the dual and opposing facets of estrogen necessitates a clear understanding to diminish the controversy of estrogen regulation in averting the systemic, autoimmune, joint degrading disorder, and 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, nuclear factor kappa B, and other regulatory proteins like matrix metalloproteinases impeding joint erosion and cartilage degradation. Estrogen modulates cellular signaling associated with inflammation, oxidative stress, related cardiovascular risk, and miRNA regulation during RA progression. Studies determining estrogen regulation in RA complicate the resemblance of the outcome as they represent both hyper and hypo level of estrogen is linked to the disease. Although some reports deliver estrogen as malign, there is now increasing evidence of rendering protection dose dependently. Variation in estrogen level causes differential expression of certain proteins and their related signaling which is 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 estrogen deficiency and treatment. Construction of protein-protein interaction network, GO, and KEGG pathway enrichment analysis of the differentially expressed proteins assist in hypothesizing a potential molecular mechanism of estrogen in RA via in silico studies. Targeting these differential proteins can emerge a new path for developing advanced therapeutic strategies.