Osteoporosis and accelerated systemic bone loss is a result of dysregulated bone turnover in form of reduced bone resorption and increased bone formation. Osteoblasts are bone forming cells that build extracellular matrix and help mineralization. Knowledge about key signaling pathways and proteins influencing bone formation, such as sclerostin and parathyroid hormone, has been translated into anabolic osteoporosis treatments.
A recent paper (“Inhibition of Cdk5 increases osteoblast differentiation and bone mass and improves fracture healing”) by Ahmad et al describes a novel cell based RNAi high content method which screens RNAi libraries of kinases in primary murine calvarial osteoblasts to look for potential novel bone formation regulators. Using this method, the research group has identified cyclin-dependant kinase 5 (Cdk5) as suppressor of osteoblast differentiation and mineralization in murine and human preosteoblastic cells. Roscovitine, a small molecule, inhibits Cdk5 and was shown to increase osteoblast formation in vitro and in vivo. Micro-CT analyses showed that mice, treated with roscovitine had enhanced bone mass and better fracture healing properties after femur osteotomy than vehicle treated mice. Importantly Cdk5 inhibition did not seem to influence osteoclastogenesis in vivo. Further analyses looking into the mechanism of Cdk5 modulation suggests that Cdk5 regulates osteoblast differentiation through MAP kinase pathway modulation.
These new findings may be of great clinical importance as Cdk5 could be a potential therapeutic target to treat osteoporosis and/or enhance fracture healing in future.