Positive regulation of osteoclastogenesis by PRIP
Research Medicine/Dentistry/Pharmaceutical Sciences
Bones are important not only because they provide structure and support for an organism’s body, but also act as an endocrine organ that regulate a number of metabolic processes. The research group of Associate Professor Miho Matsuda recently showed that PRIP*1 gene knockout (KO) in mice*2 increases bone formation and concomitantly decreases bone resorption, resulting in increased bone mineral density and trabecular bone volume. However, the role of PRIP in osteoclastogenesis has not yet been fully elucidated. Here, the author aimed to identify the effects of PRIP on bone remodeling by investigating the tooth movement in mice fitted with orthodontic devices. The extent of tooth movement was smaller in the PRIP-KO mice than in wild-type mice. Fewer osteoclasts were observed on the bone resorption side in the maxillary bones of PRIP-KO mice. Lower osteoclast differentiation was observed in the bone marrow cells that were isolated from these mice. The expression of genes that are involved in osteoclast differentiation were exhibited to a lesser extent in immature PRIP-KO cells when compared to those of wild-type mice. The PRIP-KO cells also displayed fewer changes in intracellular Ca2+ and reduced nuclear localization of a transcription factor NFATc1 which is a master regulator of osteoclastogenesis. Up-regulation of intracellular Ca2+ restored osteoclastogenesis of the PRIP-KO cells. These results indicate that PRIP positively regulates osteoclast differentiation through calcium-calcineurin-NFATc1 signaling via regulating intracellular Ca2+.
The above result has been published online on March 24th 2017 (US Time) in Journal of Biological Chemistry (‘Phospholipase C-related, but catalytically inactive protein (PRIP) upregulates osteoclast differentiation via calcium-calcineurin-NFATc1 signaling’).
PRIP*1: Phospholipase C-Related but catalytically Inactive Protein
PRIP gene knockout(KO)in mice *2: the condition of genes in all tissues being knocked out; the PRIP gene-deficient mice
Journal ReferencesPhospholipase C-related but catalytically inactive proteins regulate ovarian follicle development ,The Journal of Biological Chemistry,