Progressive ankylosis protein (ANK) in osteoblasts and osteoclasts controls bone formation and bone remodeling
Open Access
- 30 July 2010
- journal article
- research article
- Published by Oxford University Press (OUP) in Journal of Bone and Mineral Research
- Vol. 25 (8), 1771-1783
- https://doi.org/10.1002/jbmr.60
Abstract
The progressive ankylosis gene (ank) encodes a transmembrane protein that transports intracellular inorganic pyrophosphate (PPi) to the extracellular milieu. ank/ank mice, which express a truncated nonfunctional ANK, showed a markedly reduced bone mass, bone-formation rate, and number of tartrate-resistant acid phosphatase–positive (TRAP+) multinucleated osteoclasts. ANK function deficiency suppressed osteoblastic differentiation of ank/ank bone marrow stromal cells, as indicated by the decrease in the expression of bone marker genes, including osterix, reduced alkaline phosphatase activity, and mineralization. Runx2 gene expression levels were not altered. Conversely, overexpression of ANK in the preosteoblastic cell line MC3T3-E1 resulted in increased expression of bone marker genes, including osterix. Whereas runx2 expression was not altered in ANK-overexpressing MC3T3-E1 cells, runx2 transcriptional activity was increased. Extracellular PPi or Pi stimulated osteoblastogenic differentiation of MC3T3-E1 cells or partially rescued delayed osteoblastogenic differentiation of ank/ank bone marrow stromal cells. A loss of PPi transport function ANK mutation also stimulated osteoblastogenic differentiation of MC3T3-E1 cells. Furthermore, ANK function deficiency suppressed the formation of multinucleated osteoclasts from ank/ank bone marrow cells cultured in the presence of macrophage colony-stimulating factor and receptor activator of nuclear factor-κB ligand. In conclusion, ANK is a positive regulator of osteoblastic and osteoclastic differentiation events toward a mature osteoblastic and osteoclastic phenotype. © 2010 American Society for Bone and Mineral ResearchKeywords
This publication has 48 references indexed in Scilit:
- Introduction of a Phe377del Mutation in ANK Creates a Mouse Model for Craniometaphyseal DysplasiaJournal of Bone and Mineral Research, 2009
- OsteopetrosisOrphanet Journal of Rare Diseases, 2009
- Efficient osteoblast differentiation from mouse bone marrow stromal cells with polylysin-modified adenovirus vectorsBiochemical and Biophysical Research Communications, 2009
- Connexin 43 Is Required for the Anti-Apoptotic Effect of Bisphosphonates on Osteocytes and Osteoblasts In VivoJournal of Bone and Mineral Research, 2008
- Akt1 in Osteoblasts and Osteoclasts Controls Bone RemodelingPLOS ONE, 2007
- Biochemical and Genetic Analysis of ANK in Arthritis and Bone DiseaseAmerican Journal of Human Genetics, 2006
- Physiologic and pathologic functions of the NPP nucleotide pyrophosphatase/phosphodiesterase family focusing on NPP1 in calcificationPurinergic Signalling, 2006
- Retinoic acid stimulates annexin-mediated growth plate chondrocyte mineralizationThe Journal of cell biology, 2002
- Craniometaphyseal dysplasia with increased bone turnover and secondary hyperparathyroidism: Therapeutic effect of calcitoninThe Journal of Pediatrics, 1988
- Treatment of craniometaphyseal dysplasia with calcitriolThe Journal of Pediatrics, 1988