Abstract
There is a growing interest in cell therapies using mesenchymal stromal cells (MSCs) for repairing bone defects. MSCs have the ability to differentiate into osteoprogenitors and osteoblasts as well as to form calcified bone matrix. However, the molecular mechanisms governing mineralization during osteogenic differentiation remain unclear. Non-collagenous proteins in the extracellular matrix are believed to control different aspects of the mineralization. Since osteocalcin is the most abundant non-collagenous bone matrix protein, the purpose of this study is to investigate the roles of osteocalcin in mineral species production during osteogenesis of MSCs. Using Raman spectroscopy, we found that the maturation of mineral species was affected by osteocalcin expression level. After osteocalcin was knocked down, the mineral species maturation was delayed and total hydroxyapatite was lower than the control group. In addition, the expression of osteogenic marker genes, including RUNX2, alkaline phosphatase, type I collagen, and osteonectin, was downregulated during osteogenic differentiation compared to the control group; whereas gene expression of osterix was upregulated after the knockdown. Together, osteocalcin plays an essential role for the maturation of mineral species and modulates osteogenic differentiation of MSCs. The results offer new insights into the enhancement of new bone formation, such as for the treatments of osteoporosis and fracture healing.
Highlights
Mesenchymal stromal/stem cells (MSCs) are multipotent stem cells with a high capacity for self-renewal
We have developed a protocol using Raman spectroscopy to evaluate the maturation of MSCs-derived osteoblasts by monitoring the production of different mineral matrices, including hydroxyapatite, octacalcium phosphate, and β-tricalcium phosphate
We hypothesize that osteocalcin mediates hydroxyapatite formation during osteogenic maturation in MSCs and the aim of this study is to investigate the role of osteocalcin in mineralization and osteogenic maturation of MSCs
Summary
Mesenchymal stromal/stem cells (MSCs) are multipotent stem cells with a high capacity for self-renewal. When specific culture conditions and proper stimuli are applied in vitro, MSCs can differentiate into the cells of non-mesenchymal origin like hepatocytes and neuron cells [5]. These cells have the potential for cell therapy [7] and possess advantages in clinical applications, such as less ethical issues compared to embryonic stem cells and lack of teratoma-forming ability when transplanted in vivo [8]. Various lines of study have indicated that MSCs play a crucial role in bone formation and remodeling [9]
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