NDLI: The p38α MAPK positively regulates osteoblast function and postnatal bone acquisition

Content Provider	Springer Nature Link
Author	Thouverey, Cyril Caverzasio, Joseph
Copyright Year	2012
Abstract	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 p38α 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 p38α in regulating osteoblast function and bone homeostasis, we generated mice lacking p38α 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 p38α showed impaired marker gene expressions and defective mineralization in vitro. These findings indicate that p38α is an essential positive regulator of osteoblast function and postnatal bone formation in vivo.
Starting Page	3115
Ending Page	3125
Page Count	11
File Format	PDF
ISSN	1420682X
Journal	Cellular and Molecular Life Sciences
Volume Number	69
Issue Number	18
e-ISSN	14209071
Language	English
Publisher	SP Birkhäuser Verlag Basel
Publisher Date	2012-04-20
Publisher Place	Basel
Access Restriction	Subscribed
Subject Keyword	p38α MAPK Osteoblast Bone formation Postnatal Biomedicine general Life Sciences Cell Biology Biochemistry
Content Type	Text
Resource Type	Article
Subject	Cell Biology Molecular Biology Molecular Medicine Pharmacology Cellular and Molecular Neuroscience

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