The authors appreciate the generous support given by fellow laboratory members in the Department of Molecular and Medical Genetics, Oregon Health & Science University. Partial funding was provided by the National Institutes of Health (Grant no. P20 MD003350) and the Collins Medical Trust.
ISRN Biomedical Engineering
Bones -- Growth -- Effect of VItamin D on, Extracellular matrix, Vitamin D3 -- Metabolism
Osteoblastic precursors experience distinct stages during differentiation and bone development, which include proliferation, extracellular matrix (ECM) maturation, and ECM mineralization. It is well known that vitamin D plays a large role in the regulation of bone mineralization and homeostasis via the endocrine system. The activation of vitamin D requires two sequential hydroxylation steps, first in the kidney and then in the liver, in order to carry out its role in calcium homeostasis. Recent research has demonstrated that human-derived mesenchymal stem cells (MSCs) and osteoblasts can metabolize the immediate vitamin D precursor 25- dihydroxyvitamin D₃(25OH₂D₃) to the active steroid 1α,25-dihydroxyvitamin D₃ (1,25OH₂D₃) and elicit an osteogenic response. However, reports of extrahepatic metabolism of vitamin D₃, the parental vitamin D precursor, have been limited. In this study, we investigated whether osteoblast precursors have the capacity to convert vitamin D₃to 1,25OH₂D₃ and examined the potential of vitamin D3 to induce 1,25OH₂D₃ associated biological activities in osteoblast precursors. It was demonstrated that the engineered osteoblast precursor derived from human marrow (OPC1) is capable of metabolizing vitamin D₃ to 1,25OH₂D₃ in a dose- dependent manner. It was also demonstrated that administration of vitamin D₃ leads to the increase in alkaline phosphatase (ALP) activity associated with osteoblast ECM maturation and calcium deposits and a decrease in cellular proliferation in both osteoblast precursor cell lines OPC1 and MC3T3-E1. These findings provide a two-dimensional culture foundation for future three- dimensional engineered tissue studies using the OPC1 cell line.
Shelley S. Mason, et al., Extrahepatic 25-Hydroxylation of Vitamin D3 in an Engineered Osteoblast Precursor Cell Line Exploring the Influence on Cellular Proliferation and Matrix Maturation during Bone Development, ISRN Biomedical Engineering, vol. 2013, Article ID 956362