Published In

Journal of Endocrinology and Metabolism

Document Type

Article

Publication Date

4-2014

Subjects

Cell and tissue specializations, Osteointegration, Mesenchymal stem cells, Cholecalciferol

Abstract

Background: Multipotential precursor cell lines derived from human bone marrow, capable of differentiating into cartilage or bone, may provide a useful tissue development model for studying the regulation and metabolism of putative growth and differentiation factors necessary for tissue regeneration. In mammals, the process of bone development depends on the proliferation and differentiation of osteoblast lineage cells, and the subsequent synthesis and mineralization of bone extracellular matrix (ECM). Vitamin D metabolites play a pivotal role in bone and mineral homeostasis, and are positive factors on bone development. Recently, it was demonstrated that a human-derived engineered osteoblast precursor cell line (OPC1), derived from human bone marrow, can metabolize the parental precursor vitamin D3 (vitaD3) to the active steroid 1alpha,25-dihydroxyvitamin D3 (1,25OH2D3), and elicit an osteogenic response that results in the decrease in proliferation and increase in ECM synthesis during early bone development. The aim in this study is to characterize gene expression, matrix production and mineralization within a bone development model.

Methods: We investigated whether vitaD3 influences bone ECM mineralization in the same manner as 1,25OH2D3 in confluent cultures of OPC1s. In addition, we explored the influence of vitamin D metabolites, in combination with other commonly used osteogenic factors, ascorbic acid, beta-glycerophosphate, dexamethasone (dex) and recombinant human bone morphogenetic protein-2 (rhBMP-2) on the osteoinduction of OPC1.

Results: It was demonstrated that OPC1 expresses the mRNA for the enzymatic equipment necessary to convert vitaD3 to 1,25OH2D3, as well as the mRNA expression of the catabolic enzyme known to regulate the concentration of active 1,25OH2D3. It was also demonstrated that mRNA expression for the vitamin D receptor (VDR) was influenced by both vitaD3 and 1,25OH2D3. Differential results using vitamin D metabolites in combination with ascorbic acid, beta-glycerophosphate, dex and/or rhBMP-2 were observed in alkaline phosphatase (ALP) activity and calcium deposition, and mRNA expression of procollagen type I (proColI), osteocalcin (OC) and osteopontin (OP).

Conclusions: Overall it was demonstrated that vitamin D in combination with osteogenic factors influences the temporal bone development sequence in a positive manner.

Description

Copyright 2014 The authors. Published by Elmer Press.

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The original instance can be found at the publishers web site. www.jofem.org

http://dx.doi.org/10.14740/jem212w

DOI

10.14740/jem212w

Persistent Identifier

http://archives.pdx.edu/ds/psu/12056

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