| First Author | Thouverey C | Year | 2012 |
| Journal | Cell Mol Life Sci | Volume | 69 |
| Issue | 18 | Pages | 3115-25 |
| PubMed ID | 22527716 | Mgi Jnum | J:330481 |
| Mgi Id | MGI:6872457 | Doi | 10.1007/s00018-012-0983-8 |
| Citation | Thouverey C, et al. (2012) The p38alpha MAPK positively regulates osteoblast function and postnatal bone acquisition. Cell Mol Life Sci 69(18):3115-25 |
| abstractText | Bone continuously remodels throughout life by coordinated actions of osteoclasts and osteoblasts. Abnormalities in either osteoclast or osteoblast functions lead to bone disorders. The p38 MAPK pathway has been shown to be essential in controlling osteoblast differentiation and skeletogenesis. Although p38alpha is the most abundant p38 member in osteoblasts, its specific individual contribution in regulating postnatal osteoblast activity and bone metabolism is unknown. To elucidate the specific role of p38alpha in regulating osteoblast function and bone homeostasis, we generated mice lacking p38alpha in differentiated osteoblasts. Osteoblast-specific p38a knockout mice were of normal weight and size. Despite non-significant bone alterations until 5 weeks of age, mutant mice demonstrated significant and progressive decrease in bone mineral density from that age. Adult mice deficient in p38a in osteoblasts displayed a striking reduction in cancellous bone volume at both axial and appendicular skeletal sites. At 6 months of age, trabecular bone volume was reduced by 62% in those mice. Mutant mice also exhibited progressive decrease in cortical thickness of long bones. These abnormalities correlated with decreased endocortical and trabecular bone formation rate and reduced expressions of type 1 collagen, alkaline phosphatase, osteopontin and osteocalcin whereas bone resorption and osteoclasts remained unaffected. Finally, osteoblasts lacking p38alpha showed impaired marker gene expressions and defective mineralization in vitro. These findings indicate that p38alpha is an essential positive regulator of osteoblast function and postnatal bone formation in vivo. |
