MicroRNA-214-5p/TGF-β/Smad2 signaling alters adipogenic differentiation of bone marrow stem cells in postmenopausal osteoporosis

Abstract Human bone marrow stem cells (BMSCs) are heterogeneous progenitor cells with two defining features, self-renew and multi-lineage differentiation. As one of the differentiation directions, osteogenesis is vital for bone homeostasis. A growing body of evidences show that ubiquitin-dependent protein degradation plays an essential role in the osteogenic differentiation of BMSCs. In this study, we found that LMCD1 was upregulated during osteogenic differentiation process of BMSCs by analyzing GSE80614. In vitro and in vivo functional studies confirmed that LMCD1 was critical to the osteogenic commitment of BMSCs. Compared to those of the controls, downregulation of LMCD1 significantly restrained osteogenic differentiation and enhanced adipogenic differentiation, while upregulation of LMCD1 increased the osteogenic differentiation and suppressed adipogenic differentiation. Mechanically, we found that LMCD1 could protect RUNX2 and Smad1 protein from Smurf1-induced ubiquitination degradation thereby regulating BMP signaling. In conclusion, our findings suggest that LMCD1 is a novel regulator of osteogenic differentiation and may be a potential therapeutic target for bone metabolism related diseases.

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Low magnitude high frequency vibration promotes adipogenic differentiation of bone marrow stem cells via P38 MAPK signal

PLoS ONE ◽

10.1371/journal.pone.0172954 ◽

2017 ◽

Vol 12 (3) ◽

pp. e0172954 ◽

Cited By ~ 7

Author(s):

Qian Zhao ◽

Yuezhi Lu ◽

Haiyang Yu ◽

Xueqi Gan

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

P38 Mapk ◽

High Frequency ◽

Adipogenic Differentiation ◽

Bone Marrow Stem Cells ◽

High Frequency Vibration ◽

Low Magnitude

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The influence of age and osteoporosis on bone marrow stem cells from rats

Bone and Joint Research ◽

10.1302/2046-3758.74.bjr-2017-0302.r1 ◽

2018 ◽

Vol 7 (4) ◽

pp. 289-297 ◽

Cited By ~ 11

Author(s):

A. Sanghani-Kerai ◽

L. Osagie-Clouard ◽

G. Blunn ◽

M. Coathup

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Osteogenic Differentiation ◽

Adipogenic Differentiation ◽

Bone Marrow Stem Cells ◽

Female Rats ◽

Alizarin Red ◽

Young Rat ◽

Cd Marker

Objectives This study aimed to assess the effect of age and osteoporosis on the proliferative and differentiating capacity of bone-marrow-derived mesenchymal stem cells (MSCs) in female rats. We also discuss the role of these factors on expression and migration of cells along the C-X-C chemokine receptor type 4 (CXCR-4) / stromal derived factor 1 (SDF-1) axis. Methods Mesenchymal stem cells were harvested from the femora of young, adult, and osteopenic Wistar rats. Cluster of differentiation (CD) marker and CXCR-4 expression was measured using flow cytometry. Cellular proliferation was measured using Alamar Blue, osteogenic differentiation was measured using alkaline phosphatase expression and alizarin red production, and adipogenic differentiation was measured using Oil red O. Cells were incubated in Boyden chambers to quantify their migration towards SDF-1. Data was analyzed using a Student’s t-test, where p-values < 0.05 were considered significant. Results CD marker expression and proliferation of the MSCs from the three groups was not significantly different. The young MSCs demonstrated significantly increased differentiation into bone and fat and superior migration towards SDF-1. The migration of SDF-1 doubled with young rats compared with the adult rats (p = 0.023) and it was four times higher when compared with cells isolated from ovariectomized (OVX) osteopenic rats (p = 0.013). Conclusion Young rat MSCs are significantly more responsive to osteogenic differentiation, and, contrary to other studies, also demonstrated increased adipogenic differentiation compared with cells from adult and ostopenic rats. Young-rat-derived cells also showed superior migration towards SDF-1 compared with MSCs from OVX and adult control rats. Cite this article: A. Sanghani-Kerai, L. Osagie-Clouard, G. Blunn, M. Coathup. The influence of age and osteoporosis on bone marrow stem cells from rats. Bone Joint Res 2018;7:289–297. DOI: 10.1302/2046-3758.74.BJR-2017-0302.R1.

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