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. Author manuscript; available in PMC: 2022 Jan 1.
Published in final edited form as: Bone. 2020 Oct 24;142:115709. doi: 10.1016/j.bone.2020.115709

Figure 1. Proposed model for regulation of chondrocyte hypertrophy.

Figure 1.

The pathways in red letters drive chondrocyte hypertrophy. The pathways in blue letters inhibit chondrocyte hypertrophy. Chondrocyte hypertrophy is determined by the balance between the actions of Mef2 and HDAC4. Mef2 drives chondrocyte hypertrophy both by direct action and by activating Runx2 expression. Sik3 phosphorylates the 14-3-3 binding sites of HDAC4, which keeps HDAC4 in cytoplasm and subsequently inhibits HDAC4 to access Mef2 in nucleus. PTHrP inhibits the Mef2 action by releasing HDAC4 from 14-3-3. PTHrP reduces Sik3 activity through phosphorylation of PKA target sites on Sik3.