Protein kinase D1 is essential for bone acquisition during pubertal growth

Jeffery J. Ford, Lee Chuan C. Yeh, Eric C. Schmidgal, Jason F. Thompson, Martin L. Adamo, John C. Lee

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Bone formation and maintenance represents the summation of the balance of local and endocrine hormonal stimuli within a complex organ. Protein kinase D (PKD) is a member of the Ca2+/calmodulin- dependent kinase superfamily of serine/threonine kinases and has been described as the crossroads for the bone morphogenetic protein (BMP)-IGF-I signaling axis, which plays a major role in bone formation. The current study exploits the PKD1-deficient mouse model to examine the role of PKD in vivo in the skeleton. Dual-energy x-ray absorptiometry scan analysis of male and female pubescent mice demonstrated significantly decreased bone mineral density in the whole body and femoral bone compartments of PKD1 (+/-) mice, compared with their wild-type littermates. The body weight, nasal-anal length, and percentage body fat of the mice were not significantly different from their wild-type littermates. Cultured bone marrow stromal cells from PKD1 (+/-) mice demonstrated lower alkaline phosphatase activity in early differentiating osteoblasts and decreased mineralized nodule formation in mature osteoblasts. Quantitative RT-PCR analysis of osteoblast differentiation markers and osteoclast markers exhibited lower levels of expression in PKD1 (+/-) male mice than wild type. In female mice, however, only markers of osteoblast differentiation were reduced. PKD1 (+/-) mice also demonstrated a profound reduction in mRNA expression levels of BMP type II receptor and IGF-I receptor and in BMP-7 responsiveness in vitro. Together these data suggest that in mice, PKD1 action contributes to the regulation of osteoblastogenesis by altering gene expression with gender-specific effects on osteoclastogenesis, subsequently affecting skeletal matrix acquisition during puberty.

Original languageEnglish (US)
Pages (from-to)4182-4191
Number of pages10
JournalEndocrinology
Volume154
Issue number11
DOIs
StatePublished - Nov 1 2013

ASJC Scopus subject areas

  • Endocrinology

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