Parathyroid hormone regulates histone deacetylases in osteoblasts.

Parathyroid hormone (PTH) functions as an essential regulator of calcium homeostasis and as a mediator of bone remodeling. We have already shown that PTH stimulates the expression of matrix metalloproteinase-13 (MMP-13), which is responsible for degrading components of extracellular matrix. We have hypothesized that histone deacetylases (HDACs) are involved with PTH-induced MMP-13 gene expression in the osteoblastic cell line, UMR 106-01. We have shown that PTH profoundly regulates HDAC4 in UMR 106-01 cells through a PKA-dependent pathway, leading to removal of HDAC4 from the MMP-13 promoter and its enhanced transcription. Understanding the mechanism of how HDACs affect osteoblast differentiation and mineralization will identify new theraupeutic methods for bone diseases, such as osteoporosis and multiple myeloma.