Cx43- and Smad-Mediated TGF-β/ BMP Signaling Pathway Promotes Cartilage Differentiation of Bone Marrow Mesenchymal Stem Cells and Inhibits Osteoblast Differentiation

Zhang, Yadong; Zhao, Shichang; Zhu, Zhenfang; Wang, Yifei; Liu, Jianxiang; Zhang, Zhicai; Xue, Feng

doi:10.1159/000478957

Cited by 30 publications

(23 citation statements)

References 44 publications

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“…Inflammatory bone loss is characterized by decreased bone formation and increased bone uptake, and LPS induces inflammatory responses and stimulates cytokine production such as IL‐1, IL‐6, and NO, ultimately resulting in bone loss and osteoporosis (Bandow et al, ). Osteoblasts responsible for the synthesis and mineralization of bone matrix regulate bone formation by secretion of ALP, OPN, and Collagen1, and ALP is a key enzyme involved in osteoblast differentiation (Naruphontjirakul, Porter, & Jones, ; Zhang et al, ). In this study, the effects of THF on LPS‐stimulated MC3T3‐E1 osteoblast‐like cells were assessed by Alizarin Red staining (Figure a) and ALP activity (Figure b).…”

Section: Resultsmentioning

confidence: 99%

“…ALP activity and mineralization cell cycle of osteoblastic MC3T3-E1 cells damaged by lipopolysaccharide (LPS; b). MC3T3-E1 were exposed to LPS and THF for 3 days [Colour figure can be viewed at wileyonlinelibrary.com] matrix regulate bone formation by secretion of ALP, OPN, and Colla-gen1, and ALP is a key enzyme involved in osteoblast differentiation (Naruphontjirakul, Porter, & Jones, 2017;Zhang et al, 2017). In this study, the effects of THF on LPS-stimulated MC3T3-E1 osteoblastlike cells were assessed by Alizarin Red staining ( Figure 9a) and ALP activity ( Figure 9b).…”

Section: Effect Of Thf On Bone Formation Of Osteoblasts Stimulated mentioning

confidence: 99%

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6,7,4′‐Trihydroxyflavone inhibits osteoclast formation and bone resorption in vitro and in vivo

Kim

Lee

et al. 2019

Phytotherapy Research

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The balance between the osteoblasts and the osteoclasts is important for the maintenance of the skeleton of the human body. The osteoclasts absorb bone after differentiated into polymorphonuclear cells by the fusion of monocytes/macrophages. We have found that 6,7,4′‐Trihydroxyflavone (THF), a compound from the heartwood of Dalbergia Odorifera inhibits receptor activator of NF‐κB ligand (RANKL)‐induced osteoclast differentiation, actin ring formation, and bone resorption in RAW 264.7 cells and bone marrow macrophage. THF significantly inhibited the c‐Jun‐N‐terminal kinase signaling pathway without affecting extracellular signal‐regulated kinase, p38, and AKT signaling. Moreover, THF inhibited the expression of c‐Fos, nuclear factor‐activated T cells cytoplasm 1, cathepsin K, and c‐src by RANKL. We used a lipopolysaccharide (LPS)‐induced bone loss model in mice. Consequently, bone volume per tissue volume, trabecular number's reduction was recovered in THF‐treated mice, and trabecular separation's augmentation was also attenuated by THF administration. In summary, THF inhibits RANKL‐induced osteoclast differentiation by MAPK signaling pathway and inhibits bone resorption by destroying the actin ring in mature osteoclasts. THF also prevented LPS‐induced bone loss in a mice model. Thus, THF may be useful in the treatment of bone diseases associated with excessive osteoclast differentiation and bone resorption.

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Section: Resultsmentioning

confidence: 99%

Section: Effect Of Thf On Bone Formation Of Osteoblasts Stimulated mentioning

confidence: 99%

6,7,4′‐Trihydroxyflavone inhibits osteoclast formation and bone resorption in vitro and in vivo

Kim

Lee

et al. 2019

Phytotherapy Research

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“…The human bone marrow-derived mesenchymal stem cells (hBMSCs), a type of pluripotent stem cells, were the first members of the mesenchymal stem cell (MSC) family to be identified [5]. As the progenitor cells of osteoblasts, hBMSCs play a critical role in bone formation and differentiation, becoming an excellent source of seed cells in bone tissue engineering [2,6,7].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-223 Suppresses Osteoblast Differentiation by Inhibiting DHRS3

Zhang

Liu

Zheng

et al. 2018

Cell Physiol Biochem

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Background/Aims: In this study, we aimed to use bioinformatics tools to identify the specific miRNAs and mRNAs involved in osteogenic differentiation and to further explore the way in which miRNA regulates osteogenic differentiation. Methods: The microarray GSE80614, which includes data from 3 human mesenchymal stromal cells (hMSCs) and 3 hMSCs after 72 hours (hr) of osteogenic differentiation, was used to screen for differentially expressed mRNAs. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of these mRNAs were conducted using Gene Set Enrichment Analysis (GSEA). Then, the miRanda website was employed to detect the binding sites of DHRS3. In vitro experiments, including RT-PCR and western blotting, were used to detect miR-233 and DHRS3 expression levels 7 and 14 days (d) after the induction of osteogenic differentiation using human bone marrow-derived mesenchymal stem cells (hBMSCs). The target relationship between miR-223 and DHRS3 was confirmed by a dual luciferase assay. ALP (alkaline phosphatase) staining, ARS (Alizarin Red S) staining and western blotting (Runx2, OPN, OCN) were used to detect the level of osteogenic differentiation after transfection with miR-223 mimics and DHRS3 cDNA. Results: In this study, 127 mRNAs differentially expressed during osteogenic differentiation were identified in GSE80614. GO term and KEGG pathway enrichment analyses found that the retinol metabolism pathway was activated during osteogenic differentiation and that DHRS3, which is involved in the pathway, was upregulated. During osteogenic differentiation in hBMSCs, miR-223 was gradually downregulated, while DHRS3 was upregulated. After 14 days of osteogenic differentiation, ALP and ARS staining assay results showed strong ALP activity and extracellular matrix calcification with the inhibition of miR-223 or the overexpression of DHRS3. Furthermore, the expression levels of Runx2, OPN, and OCN were upregulated with the knockdown of miR-223 or the overexpression of DHRS3, while the simultaneous transfection of a miR-223 agomir and DHRS3 cDNA resulted in no significant difference from the negative control (NC) group. Conclusion: The inhibition of miR-223 promotes the osteogenic differentiation of hBMSCs via the upregulation of DHRS3.

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“…Olive-derived polyphenols including oleuropein impair adipogenesis and enhance the chondrogenic and osteogenic ability of hMSCs. Cx43, altered during OA 27 , is also a critical regulator of hMSCs differentiation [44][45][46] . Based on previous reported results from our group 4, 27,30,47,48 , we used a small-scale screening to identify compounds that downregulate Cx43 (data not shown), and we have identified compounds such as the small molecule oleuropein (Fig.…”

Section: Resultsmentioning

confidence: 99%

Senolytic activity of small molecular polyphenols from olive restores chondrocyte redifferentiation and cartilage regeneration in osteoarthritis

Varela‐Eirin

Varela-Vázquez

Paı́no

et al. 2019

Preprint

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Cx43- and Smad-Mediated TGF-β/ BMP Signaling Pathway Promotes Cartilage Differentiation of Bone Marrow Mesenchymal Stem Cells and Inhibits Osteoblast Differentiation

Cited by 30 publications

References 44 publications

6,7,4′‐Trihydroxyflavone inhibits osteoclast formation and bone resorption in vitro and in vivo

6,7,4′‐Trihydroxyflavone inhibits osteoclast formation and bone resorption in vitro and in vivo

MicroRNA-223 Suppresses Osteoblast Differentiation by Inhibiting DHRS3

Senolytic activity of small molecular polyphenols from olive restores chondrocyte redifferentiation and cartilage regeneration in osteoarthritis

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