TRPV4 regulates osteoblast differentiation and mitochondrial function that are relevant for channelopathy

Different ion channels present in the osteoblast regulate the cellular functions including bio-mineralization, a process that is a highly stochastic event. Cellular events and molecular signaling involved in such process is poorly understood. Here we demonstrate that TRPV4, a mechanosensitive ion channel is endogenously present in an osteoblast cell line (MC3T3-E1) and in primary osteoblasts. Pharmacological activation of TRPV4 enhanced intracellular Ca2+-level, expression of osteoblast-specific genes and caused increased bio-mineralization. TRPV4 activation also affects mitochondrial Ca2+-levels and mitochondrial metabolisms. We further demonstrate that different point mutants of TRPV4 induce different mitochondrial morphology and have different levels of mitochondrial translocation, collectively suggesting that TRPV4-mutation-induced bone disorders and other channelopathies are mostly due to mitochondrial abnormalities. These findings may have broad biomedical implications.

Automated summary

Research has found that TRPV4, a mechanosensitive ion channel, is naturally present in osteoblast cells and is involved in regulating calcium levels, gene expression, and bio-mineralization. Activation of TRPV4 also affects mitochondrial calcium levels and metabolism. Different mutations of TRPV4 have varying effects on mitochondrial morphology and translocation, suggesting that TRPV4-related bone disorders and channelopathies are often caused by mitochondrial abnormalities. These findings have significant biomedical implications.