Protein kinase Cα (PKCα) Regulates Bone Architecture and Osteoblast Activity*

Gabriel L Galea, Lee B Meakin, Christopher M Williams, Sarah L Hulin-Curtis, Lance E Lanyon, Alastair W Poole, Joanna S Price

Research output: Contribution to journalArticle (Academic Journal)peer-review

19 Citations (Scopus)
280 Downloads (Pure)

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 Prkcα-/- female but not male mice, in which bone tissue progressively invades the medullary cavity in the mid-diaphysis. This bone deposition progresses with age, is prevented by disuse, but unaffected by ovariectomy. Castration of male Prkcα-/- but not WT mice results in the formation of small amounts of intra-medullary bone. Osteoblast differentiation markers and Wnt target gene expression were up-regulated in osteoblast-like cells derived from cortical bone of female Prkcα-/- mice compared to WT. Additionally, although osteoblastic cells derived from WT proliferate following exposure to estradiol or mechanical strain, those from Prkcα-/- mice do not. Female Prkcα-/- 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 Prkcα-/- 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.

Original languageEnglish
Pages (from-to)25509-25522
Number of pages14
JournalJournal of Biological Chemistry
Volume289
Issue number37
Early online date28 Jul 2014
DOIs
Publication statusPublished - 12 Sep 2014

Keywords

  • Bone
  • Estrogen
  • Gaucher Disease
  • Osteoblast
  • Protein Kinase C (PKC)
  • Wnt Signaling
  • Mechanical Loading

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