MicroRNAs (miRNAs) emerge as important regulators of stem cell lineage commitment and bone development. MiRNA-26a (miR-26a) is one of the important miRNAs regulating osteogenic differentiation of both bone marrow-derived mesenchymal stem cells (BMSCs) and adipose tissue-derived mesenchymal stem cells (ADSCs). However, miR-26a functions oppositely in osteogenic differentiation of BMSCs and ADSCs, suggesting distinct post-transcriptional regulation of tissue-specific MSC differentiation. However, the molecular basis is largely unknown. Here, we report that the function of miR-26a is largely depended on the intrinsic signaling regulation network of MSCs. Using bioinformatics and functional assay, we confirmed that miR-26a potentially targeted on GSK3β and Smad1 to regulate Wnt and BMP signaling pathway. Overall comparative analysis revealed that Wnt signaling was enhanced more potently and played a more important role than BMP signaling in osteogenic differentiation of BMSCs, whereas BMP pathway was more essential for promoting osteogenic differentiation of ADSCs. The distinct activation pattern and role of signaling pathways determined that miR-26a majorly targeted on GSK3β to activate Wnt signaling for promoting osteogenic differentiation of BMSCs, whereas it inhibited Smad1 to suppress BMP signaling for interfering with the osteogenic differentiation of ADSCs. Taken together, our study demonstrated that BMSCs and ADSCs applied different signaling pathway to facilitate their osteogenic differentiation, which determined the inverse function of miR-26a. The distinct transcriptional regulation and post-transcriptional regulation network suggested the intrinsic molecular differences between tissue-specific MSCs and the complexity in MSC research and MSC-based cell therapy.
The interplay between osteoblasts and osteoclasts has a crucial role in maintaining bone homeostasis. In this study, we reveal that osteoblasts are capable of inducing osteoclast apoptosis by FAS ligand (FASL)/FAS signaling. Conditional knockout of FASL in osteoblasts results in elevated osteoclast numbers and activity, along with reduced bone mass, suggesting that osteoblastproduced FASL is required to maintain physiological bone mass. More interestingly, we show that osteoblasts from ovariectomized (OVX) osteoporotic mice exhibit decreased FASL expression that results from the IFN-γ-and TNF-α-activated NF-κB pathway, leading to reduced osteoclast apoptosis and increased bone resorption. Systemic administration of either IFN-γ or TNF-α ameliorates the osteoporotic phenotype in OVX mice and rescues FASL expression in osteoblasts. In addition, ovariectomy induces more significant bone loss in FASL conditional knockout mice than in control group with increased osteoclast activity in which the levels of RANKL and OPG remain unchanged. Taken together, this study suggests that osteoblast-induced osteoclast apoptosis via FASL/FAS signaling is a previously unrecognized mechanism that has an important role in the maintenance of bone mass in both physiological conditions and OVX osteoporosis.
Doctors and patients attempt to accelerate orthodontic tooth movement with a minimally invasive surgery approach. The purpose of this systematic review was to evaluate the evidence of accelerated tooth movement in minimally invasive surgery and the adverse effects from it. A systematic search of the literature was performed in the electronic databases of PubMed, CENTRAL (Cochrane Central Register of Controlled Trials), Embase, Scopus, Web of Science, Science Direct, and Medline and was complemented by a manual search until February 2019. The inclusion criteria were prospective clinical studies of patients treated with a fixed appliance, and the intervention was accelerated orthodontic treatment with minimally invasive surgery. Nineteen articles (538 participants) were included in the review: 9 studies assessed the rate of upper canine movement; 5 considered the treatment time; 1 evaluated the en masse retraction time; and 4 studied adverse effects. We performed a meta-analysis for the rate of canine movement and treatment time and described the results for the adverse effects in a systematic review. The results of the subgroup analysis according to micro-osteoperforation and piezocision were included in the study. No accelerated tooth movement was found in the micro-osteoperforation group. After flapless corticotomy procedures, increased tooth movement rates were identified by weighted mean differences of 0.63 (95%CI = 0.22, 1.03, P = 0.003) and 0.64 (95% CI, −25 to 1.53; P = 0.16) for 1 and 2 mo, respectively. The mean treatment time was 68.42 d (95% CI, −113.19 to −23.65; P = 0.003) less that than for minimally invasive surgery. Moreover, no significant adverse effect was found. Because of the high heterogeneity of the meta-analysis, the results must be validated by additional large-sample multicenter clinical trials. There is not sufficient evidence to support that the single use of micro-osteoperforation could accelerate tooth movement, and there is only low-quality evidence to prove that flapless corticotomy could accelerate tooth movement.
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