Figure 2.

Growth zone chondrocyte with plasma membrane-associated receptors (VDR and PDIA3) for 1α,25(OH)₂D₃ release matrix vesicles into the ECM that contain microRNA and matrix metalloproteinases (MMPs). Chondrocyte plasma membrane PDIA3 acts via PKCα. Matrix vesicles contain the PDIA3 receptor complexed with PKCζ. 1α,25(OH)₂D₃ binds to matrix vesicle PDIA3, activating PLA2 to release arachidonic acid and destabilize the vesicle membrane; this releases the contents into the ECM. MMP released from MVs activates latent TGFβ (LTGFβ) in the extracellular matrix removing the latent binding protein. MicroRNAs act back on the chondrocytes, but whether the microRNAs are released into the ECM or are transported to the cells via the matrix vesicles or as membrane liposomes is not known.