Fig. 2

Schematic diagram of ca²⁺ signal transduction pathway and other miscellaneous pathways activate in response to the electrical and mechanical stimulations. The mechanical stimulation on piezoelectric scaffold will result in the electrical signal generation and which will stimulate the voltage-gated ca²⁺ channel. Further increase in the intracellular Ca²⁺ concentration activates the calmodulin (an abbreviation of the calcium-modulated protein) and which will further activate the calcineurin (calcium and calmodulin-dependent serine/threonine protein phosphatase). The activated calcineurin dephosphorylates the NF-AT and it will translocate to the nucleus, where it acts in conjunction with other associated proteins as transcription factors. Also the mechanical stimulation itself can activate the mechanoreceptors present in the membrane and which will lead to the activation of PKC and MAPK signaling cascades. These cascades will result in the synthesis of proteoglycan and inhibition of IL-1, responsible for the breakdown of proteoglycan