Galea, GL;
Meakin, LB;
Williams, CM;
Hulin-Curtis, SL;
Lanyon, LE;
Poole, AW;
Price, JS;
(2014)
Protein kinase Cα (PKCα) regulates bone architecture and osteoblast activity.
J Biol Chem
, 289
(37)
pp. 25509-25522.
10.1074/jbc.M114.580365.
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Abstract
Bones' strength is achieved and maintained through adaptation to load bearing. The role of the protein kinase PKCα in this process has not been previously reported. However, we observed a phenotype in the long bones of Prkca(-/-) female but not male mice, in which bone tissue progressively invades the medullary cavity in the mid-diaphysis. This bone deposition progresses with age and is prevented by disuse but unaffected by ovariectomy. Castration of male Prkca(-/-) but not WT mice results in the formation of small amounts of intramedullary bone. Osteoblast differentiation markers and Wnt target gene expression were up-regulated in osteoblast-like cells derived from cortical bone of female Prkca(-/-) mice compared with WT. Additionally, although osteoblastic cells derived from WT proliferate following exposure to estradiol or mechanical strain, those from Prkca(-/-) mice do not. Female Prkca(-/-) mice develop splenomegaly and reduced marrow GBA1 expression reminiscent of Gaucher disease, in which PKC involvement has been suggested previously. From these data, we infer that in female mice, PKCα normally serves to prevent endosteal bone formation stimulated by load bearing. This phenotype appears to be suppressed by testicular hormones in male Prkca(-/-) mice. Within osteoblastic cells, PKCα enhances proliferation and suppresses differentiation, and this regulation involves the Wnt pathway. These findings implicate PKCα as a target gene for therapeutic approaches in low bone mass conditions.
| Type: | Article |
|---|---|
| Title: | Protein kinase Cα (PKCα) regulates bone architecture and osteoblast activity. |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1074/jbc.M114.580365 |
| Publisher version: | http://dx.doi.org/ 10.1074/jbc.M114.580365 |
| Language: | English |
| Additional information: | Copyright © 2014 by The American Society for Biochemistry and Molecular Biology, Inc. This version is the author version of record . For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Bone, Estrogen, Gaucher Disease, Mechanical Loading, Osteoblast, Protein Kinase C (PKC), Wnt Signaling, Animals, Cell Differentiation, Cell Proliferation, Female, Humans, Male, Mice, Osteoblasts, Osteogenesis, Protein Kinase C-alpha, Weight-Bearing, Wnt Proteins |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1543957 |
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