-
Nan Yang, Guang Wang,
Chenghu Hu,
Yuanyuan Shi,
Li Liao,
Songtao Shi,
Yan Cai,
Shuli Cheng,
Xi Wang,
Yali Liu,
Liang Tang,
Yin Ding,
Yan Jin
[show abstract]
[hide abstract]
ABSTRACT: Inflammatory cytokines, especially TNF-α, have been shown to inhibit osteogenic differentiation of mesenchymal stem cells (MSCs) and bone formation in estrogen deficiency-induced osteoporosis, but the mechanism responsible remains poorly understood. MicroRNAs (miRNAs) have been shown to regulate MSC differentiation. Here, we identified a novel mechanism that TNF-α suppressing the functional axis of a key miRNA(miR-21) contributes to estrogen deficiency-induced osteoporosis. In this study, we screened a key miRNA (miR-21) that was significantly down-regulated in MSCs derived from estrogen deficiency-induced osteoporosis. The miR-21 was suppressed by TNF-α during the osteogenesis of MSCs. Furthermore, miR-21 was confirmed to promote the osteoblast differentiation of MSCs by repressing Spry1, which can negatively regulate the osteogenic differentiation of MSCs. Up-regulating miR-21 partially rescued TNF-α-impaired osteogenesis of MSCs. Blocking TNF-α ameliorated the inflammatory environment and significantly enhanced bone formation with increased miR-21 expression and suppressed Spry1 expression in ovariectomized (OVX) mice. Our results revealed a novel function for miR-21 and suggested that suppressed miR-21 may contribute to impaired bone formation by elevated TNF-α in estrogen deficiency-induced osteoporosis. This study may indicate a molecular basis for novel therapeutic strategies against osteoporosis and other inflammatory bone diseases. © 2012 American Society for Bone and Mineral Research.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 10/2012; · 6.04 Impact Factor
-
Yali Liu,
Wenjia Liu,
Chenghu Hu,
Zengfu Xue, Guang Wang,
Bofu Ding,
Hailang Luo,
Liang Tang,
Xiangwei Kong,
Xiaoyan Chen,
Na Liu,
Yin Ding,
Yan Jin
[show abstract]
[hide abstract]
ABSTRACT: Chronic inflammatory diseases, such as rheumatoid arthritis and periodontitis, are the most common causes of bone tissue destruction. Recently, human periodontal ligament tissue-derived mesenchymal stem cells (PDLSCs), a population of multipotent stem cells, have been used to reconstruct tissues destroyed by chronic inflammation. However, the impact of the local inflammatory microenvironment on tissue-specific stem cells and the mechanisms controlling the effects of the local inflammatory environment remain poorly understood. In this study, we found that the multidifferentiation potential of mesenchymal stem cells (MSCs) isolated from periodontitis-affected periodontal ligament tissue (P-PDLSCs) was significantly lower than that of MSCs isolated from healthy human periodontal ligament tissue (H-PDLSCs). Inflammation in the microenvironment resulted in an inhibition of miR-17 levels, and a perturbation in the expression of miR-17 partly reversed the differentiation potential of PDLSCs in this microenvironment. Furthermore, inflammation in the microenvironment promoted the expression of Smad ubiquitin regulatory factor one (Smurf1), an important negative regulator of MSC osteogenic differentiation. Western blotting and 3' untranslated regions (3'-UTR) reporter assays confirmed that Smurf1 is a direct target of miR-17 in PDLSCs. Our data demonstrate that excessive inflammatory cytokine levels, miR-17, and Smurf1 were all involved in a coherent feed-forward loop. In this circuit, inflammatory cytokines led to direct activation of Smurf1 and downregulation of miR-17, thereby increasing degradation of Smurf1-mediated osteoblast-specific factors. The elucidation of the molecular mechanisms governing MSC osteogenic differentiation in a chronic inflammatory microenvironment could provide us with a better knowledge of chronic inflammatory disorder and improve stem cell-mediated inflammatory bone disease therapy.
Stem Cells 09/2011; 29(11):1804-16. · 7.78 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The existence of PDLSCs [PDL (periodontal ligament) stem cells] in PDL has been identified and such cells may function in periodontal reconstruction, including bone formation. Oestrogens/ERs (oestrogen receptors; ERα and ERβ) exert important effects in bone formation, however, the relationship between ERs and PDLSCs has not been established. In the present study, PDLSCs were isolated and assays for detecting stem-cell biomarkers and multipotential differentiation potential confirmed the validity of human PDLSCs. The results of RT-PCR (reverse transcription-PCR) and Western blotting showed that ERα and ERβ were expressed at higher levels in PDLSCs as compared with PDLCs (PDL cells), and 17β-oestradiol obviously induced the osteogenic differentiation of PDLSCs in vitro. Furthermore, a pan-ER inhibitor or lentivirus-mediated siRNA (small interfering RNA) targeting ERα or ERβ blocked the oestrogen-induced osteogenic differentiation of PDLSCs. The results indicate that both ERα and ERβ were involved in the process of osteogenic differentiation of PDLSCs.
Bioscience Reports 04/2011; 31(2):117-24. · 2.38 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To investigate the effect of estrogen receptor beta (ERbeta) on osteoblastic differentiation function of human periodontal ligament (hPDL) cells by measuring the alkaline phosphatase (ALP) activity and the production of osteocalcin (OCN) in vitro.
We employed a short interfering RNA (siRNA) technique to inhibit ERbeta expression in hPDL cells; the cells were cultured with a saturating concentration of 17beta-estradiol (10(-7)M). ALP activity was analysed by colorimetric assay using ALP kit and the amount of OCN was assessed by osteocalcin ELISA kit.
It was shown that estradiol significantly enhanced the ALP activity and the production of OCN in hPDL cells. However, the ALP activity and the production of OCN in hPDL-siERbeta cells were not significantly changed after estradiol treatment.
These results indicate that ERbeta may play important roles in estrogen-induced effects on osteoblastic differentiation function of PDL cells and estrogen influences the bone formation capacity of PDL cells mainly via ERbeta.
Archives of Oral Biology 07/2008; 53(6):553-7. · 1.60 Impact Factor
