title: Protein kinase Cα (PKCα) regulates bone architecture and osteoblast activity.
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.
authors: From the School of Veterinary Sciences, University of Bristol, Bristol BS2 8EJ, United Kingdom and gabriel.galea@bristol.ac.uk.
authors: Gabriel L
authors: GL
authors: Galea
authors: From the School of Veterinary Sciences, University of Bristol, Bristol BS2 8EJ, United Kingdom and.
authors: Lee B
authors: LB
authors: Meakin
authors: the School of Physiology and Pharmacology, University of Bristol, Bristol BS8 1TD, United Kingdom.
authors: Christopher M
authors: CM
authors: Williams
authors: From the School of Veterinary Sciences, University of Bristol, Bristol BS2 8EJ, United Kingdom and.
authors: Sarah L
authors: SL
authors: Hulin-Curtis
authors: From the School of Veterinary Sciences, University of Bristol, Bristol BS2 8EJ, United Kingdom and.
authors: Lance E
authors: LE
authors: Lanyon
authors: the School of Physiology and Pharmacology, University of Bristol, Bristol BS8 1TD, United Kingdom.
authors: Alastair W
authors: AW
authors: Poole
authors: From the School of Veterinary Sciences, University of Bristol, Bristol BS2 8EJ, United Kingdom and.
authors: Joanna S
authors: JS
authors: Price
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics*; D051571:Protein Kinase C-alpha / Q000235:genetics / Q000378:metabolism*; D016474:Weight-Bearing; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D051153:Wnt Proteins; D051571:Protein Kinase C-alpha
keywords: Bone; Estrogen; Gaucher Disease; Mechanical Loading; Osteoblast; Protein Kinase C (PKC); Wnt Signaling