Cell cycle and apoptosis regulatory protein (CARP)-1 is expressed in osteoblasts and regulated by PTH.

Bone mass is dependent on osteoblast proliferation, differentiation and life-span of osteoblasts. Parathyroid hormone (PTH) controls osteoblast cell cycle regulatory proteins and suppresses mature osteoblasts apoptosis. Intermittent administration of PTH increases bone mass but the mechanism of action are complex and incompletely understood. and Apoptosis Regulatory Protein (aka CCAR1) is a novel transducer of signaling by diverse agents including cell growth and differentiation factors. To gain further insight into the molecular mechanism, we investigated involvement of in PTH signaling in osteoblasts. Immunostaining studies revealed presence of Cduanyu37-1 in osteoblasts and osteocytes, while a minimal to absent levels were noted in the chondrocytes of femora from 10 to 12-week old mice. Treatment of 7-day differentiated MC3T3-E1 clone-4 (MC-4) mouse osteoblastic cells and primary calvarial osteoblasts with PTH for 30min to 5h followed by Western blot analysis showed 2- to 3-fold down-regulation of Cduanyu37-1 protein expression in a dose- and time-dependent manner compared to the respective vehicle treated control cells. H-89, a A inhibitor, suppressed PTH action on Cduanyu37-1 protein expression indicating mechanism. PMA, a duanyu1527 C agonist, mimicked PTH action, and the inhibitor, GF109203X, partially blocked PTH-dependent downregulation of implying involvement of U0126, a Mitogen-Activated duanyu1527 (MAPK) Kinase (MEK) inhibitor, failed to interfere with Cduanyu37-1 suppression by PTH. In contrast, SB203580, p38 inhibitor, attenuated PTH down-regulation of Cduanyu37-1 suggesting that PTH utilized an Extracellular Signal Regulated Kinase (ERK)-independent but p38 dependent pathway to regulate Cduanyu37-1 protein expression in osteoblasts. Immunofluorescence staining of differentiated osteoblasts further revealed nuclear to cytoplasmic translocation of Cduanyu37-1 protein following PTH treatment. Collectively, our studies identified Cduanyu37-1 for the first time in osteoblasts and suggest its potential role in PTH signaling and bone anabolic action.

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