Aldo-keto reductase family 1 member C1 regulates the osteogenic differentiation of human ASCs by targeting the progesterone receptor.

BACKGROUND: As a promising way to repair bone defect, bone tissue engineering has attracted a lot of attentions from researchers in recent years. Searching for new molecular target to modify the seed cells and enhance their osteogenesis capacity is one of the hot topics in this field. As a member of aldo-keto reductase family, aldo-keto reductase family 1 member C1 (AKR1C1) is reported to associate with various tumors. However, whether AKR1C1 takes part in regulating differentiation of adipose-derived mesenchymal stromal/stem cells (ASCs) and its relationship with progesterone receptor (PGR) remain unclear. METHODS: Lost-and-gain-of-function experiments were performed using knockdown and overexpression of AKR1C1 to identify its role in regulating osteogenic and adipogenic differentiation of hASCs in vitro. Heterotypic bone and adipose tissue formation assay in nude mice were used to conduct the in vivo experiment. Plasmid and siRNA of PGR, as well as western blot, were used to clarify the mechanism AKR1C1 regulating osteogenesis. RESULTS: Our results demonstrated that AKR1C1 acted as a negative regulator of osteogenesis and a positive regulator of adipogenesis of hASCs via its enzyme activity both in vitro and in vivo. Mechanistically, PGR mediated the regulation of AKR1C1 on osteogenesis. CONCLUSIONS: Collectively, our study suggested that AKR1C1 could serve as a regulator of osteogenic differentiation via targeting PGR and be used as a new molecular target for ASCs modification in bone tissue engineering.

D-mannose attenuates bone loss in mice via Treg cell proliferation and gut microbiota-dependent anti-inflammatory effects.

BACKGROUND: D-mannose exhibits strong anti-inflammatory properties, but whether it has beneficial effects on preventing and treating osteoporosis remains unknown. METHODS: Female, 12-month-old senile C57BL6/J mice (s-Man group) and 8-week-old ovariectomized C57BL6/J mice (OVX-Man group) were treated with D-mannose in drinking water for 2 months (six mice/group). Microcomputed tomography analysis and hematoxylin and eosin staining were performed to investigate the effect of D-mannose on attenuation of bone loss. Tartrate-resistant acid phosphatase staining of tissue sections, flow cytometry, enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction, and gut microbiome biodiversity tests were used to explore the underlying mechanisms. RESULTS: D-mannose-induced marked increases in cortical bone volume and trabecular bone microarchitecture in the s-Man and OVX-Man group compared with that in the s-CTRL (senile control) and OVX group, respectively. Moreover, D-mannose downregulated osteoclastogenesis-related cytokines in the bone marrow and expanded regulatory T cells in the spleen of mice. Furthermore, D-mannose reconstructed the gut microbiota and changed the metabolite composition. CONCLUSION: D-mannose attenuated bone loss induced by senility and estrogen deficiency in mice, and this effect may be mediated by D-mannose-induced proliferation of regulatory T cells and gut microbiota-dependent anti-inflammatory effects.

LAMA2 regulates the fate commitment of mesenchymal stem cells via hedgehog signaling.

BACKGROUND: Bone defects are a common clinical condition that has gained an increasing amount of attention in recent years. Causes of bone defect include tumors, inflammation, and fractures. Bone tissue engineering is a novel treatment of bone defect, and human mesenchymal stem cells (hMSCs) are the ideal seed cells for bone tissue engineering due to their multi-lineage differentiation potential and immunogenicity. The laminin α2 (LAMA2) gene encodes the α2 subunit of laminins. Mutations in this gene have been reported to cause muscular dystrophy, but thus far no studies have elucidated the role of LAMA2 in the fate choices of MSCs. Here, we aimed to investigate the critical role of LAMA2 in the osteogenesis and adipogenesis of mesenchymal stem cells (MSCs). METHODS: We investigated LAMA2 function in osteogenic and adipogenic differentiation of MSCs in vitro and in vivo through loss- and gain-of-function experiments. In addition, molecular mechanism was clarified by Western blot and siRNA. RESULTS: Our results demonstrated that LAMA2 was a critical regulator for fate commitment of MSCs. Both in vitro and in vivo studies indicate that LAMA2 inhibits osteogenesis and promotes adipogenesis. Mechanistically, we found that LAMA2 regulated osteogenesis and adipogenesis of MSCs by modulating the hedgehog signaling pathway. CONCLUSIONS: The present work confirms that LAMA2 is a new molecular target for MSC-based bone regeneration.

Complete de-Dopplerization and acoustic holography for external noise of a high-speed train.

Identification and measurement of moving sound sources are the bases for vehicle noise control. Acoustic holography has been applied in successfully identifying the moving sound source since the 1990s. However, due to the high demand for the accuracy of holographic data, currently the maximum velocity achieved by acoustic holography is just above 100 km/h. The objective of this study was to establish a method based on the complete Morse acoustic model to restore the measured signal in high-speed situations, and to propose a far-field acoustic holography method applicable for high-speed moving sound sources. Simulated comparisons of the proposed far-field acoustic holography with complete Morse model, the acoustic holography with simplified Morse model and traditional delay-and-sum beamforming were conducted. Experiments with a high-speed train running at the speed of 278 km/h validated the proposed far-field acoustic holography. This study extended the applications of acoustic holography to high-speed situations and established the basis for quantitative measurements of far-field acoustic holography.