Role of CaV1.2 in Tendon Formation
Tensile-bearing tendons are highly prone to acute injury and chronic degeneration from overuse, processes called tendinopathies. Therapeutic options for tendinopathies remain few due to limited knowledge about the basic biology underlying tendon development and postnatal tendon growth. Ca2+ signals have been implicated in tendon mechanotransduction, acting as second messengers to convert mechanical load to biochemical signals. However, Ca2+ signaling details in tendon and the source(s) of the increase in intracellular Ca2+ in tendon fibroblasts are largely unknown.
Using the CaV1.2 lacZ reporter mouse, we demonstrated robust endogenous expression of CaV1.2, a voltage-gated Ca2+ channel during tendon development and postnatal growth. Importantly, excess Ca2+ influx through the Timothy syndrome causing CaV1.2 mutant channel (gain-of-function) specifically in mouse tendons/ligaments promoted tendon and ligament formation, highlighting a previously unappreciated roles for CaV1.2 in tendon biology. We are currently investigating the molecular mechanisms and signaling cascades up/downstream of CaV1.2 that underlie tendon mechanotransduction and tendon formation.
