Fructose-bisphosphatase1 identified as a potential therapeutic target for osteoarthritis treatment

A recent study, featured in Arthritis Research and Therapy, has unveiled the crucial role of fructose-bisphosphatase1 (FBP1) in promoting polysaccharide synthesis within cartilage. This intricate process plays a pivotal role in reducing cartilage degeneration by modulating crumbs homolog 3 (CRB3). The study findings suggest that the targeted regulation of FBP1 holds promise as a potential therapeutic avenue for osteoarthritis (OA).

The study, conducted by Dr. Wang and colleagues, utilized cartilage samples from both osteoarthritis patients and C57 mice to meticulously assess the severity of OA through safranin O-fast green staining. The investigation revealed a reduction in polysaccharide levels within the cartilage, accompanied by a simultaneous decrease in FBP1 expression. In the investigative methodology, chondrocytes were exposed to IL-1β to induce osteoarthritis-like conditions in vitro. Subsequent efforts involved the overexpression of FBP1 in these chondrocytes using plasma. This intervention with FBP1 demonstrated a significant reduction of chondrocyte degeneration and senescence, as substantiated by both in vitro and in vivo experiments. The researchers further explore the downstream proteins associated with FBP1, revealing that CRB3 plays a pivotal role in suppressing chondrocyte degeneration and retarding senescence.

Accumulating evidence reports an increased incidence and severity of OA in diabetic individuals, further elucidating the systemic impact of glucose metabolism on joints. Moreover, a robust link has been established between glucose metabolism within chondrocytes and the initiation of OA, supported by multiple studies. The synthesis of glycosaminoglycans in the extracellular matrix and the gluconeogenesis pathway plays a critical role in providing a substantial quantity of glucose as a fundamental building block. Hence, understanding the underlying impact of gluconeogenesis on OA assumes paramount importance. FBP1, a key enzyme ubiquitously present in most cells, is essential for the regulation of gluconeogenesis, influencing the synthesis of glycogen and various polysaccharide substances, underscoring its significance in mediating the progression of OA.

The established connection between chondrocyte glucose metabolism and OA highlights the need for targeted interventions. The regulatory effect of FBP1 on gluconeogenesis emerges as a potential therapeutic target, offering insights for future research and therapeutic strategies.

Reference

Wang Z, Wang X, Liu L, Guo X, Zhang H, Yin J, et al. Fructose-bisphosphatase1 (FBP1) alleviates experimental osteoarthritis by regulating Protein crumbs homolog 3 (CRB3). Arthritis Res Ther. 2023 Dec 4;25(1):235.

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