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 Ca_V1.2 lacZ reporter mouse, we demonstrated robust endogenous expression of Ca_V1.2, a voltage-gated Ca²⁺ channel during tendon development and postnatal growth. Importantly, excess Ca²⁺ influx through the Timothy syndrome causing Ca_V1.2 mutant channel (gain-of-function) specifically in  mouse tendons/ligaments promoted tendon and ligament formation, highlighting a previously unappreciated roles for Ca_V1.2 in tendon biology. We are currently investigating the molecular mechanisms and signaling cascades up/downstream of Ca_V1.2 that underlie tendon mechanotransduction and tendon formation.

 

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