Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling. Here, we focused on the role of Semaphorin 3A(Sema3A), expressed by sensory nerves, in mechanical loads-induced bo...Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling. Here, we focused on the role of Semaphorin 3A(Sema3A), expressed by sensory nerves, in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement(OTM) model. Firstly, bone formation was activated after the 3rd day of OTM,coinciding with a decrease in sensory nerves and an increase in pain threshold. Sema3A, rather than nerve growth factor(NGF),highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM. Moreover, in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells(hPDLCs) within 24 hours.Furthermore, exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload. Mechanistically, Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway, maintaining mitochondrial dynamics as mitochondrial fusion. Therefore, Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation, both as a pain-sensitive analgesic and a positive regulator for bone formation.展开更多
Cell-based tissue engineering is one of the optimistic approaches to replace current treatments for bone defects.Urine-derived stem cells(USCs)are obtained non-invasively and become one of the promising seed cells for...Cell-based tissue engineering is one of the optimistic approaches to replace current treatments for bone defects.Urine-derived stem cells(USCs)are obtained non-invasively and become one of the promising seed cells for bone regeneration.An injectable BMP2-releasing chitosan microspheres/type I collagen hydrogel(BMP2-CSM/Col I hydrogel)was fabricated.USCs proliferated in a time-dependent fashion,spread with good extension and interconnected with each other in different hydrogels both for 2D and 3D models.BMP2 was released in a sustained mode for more than 28 days.Sustained-released BMP2 increased the ALP activities and mineral depositions of USCs in 2D culture,and enhanced the expression of osteogenic genes and proteins in 3D culture.In vivo,the mixture of USCs and BMP2-CSM/Col I hydrogels effectively enhanced bone regeneration,and the ratio of new bone volume to total bone volume was 38%after 8weeks of implantation.Our results suggested that BMP2-CSM/Col I hydrogels promoted osteogenic differentiation of USCs in 2D and 3D culture in vitro and USCs provided a promising cell source for bone tissue engineering in vivo.As such,USCs-seeded hydrogel scaffolds are regarded as an alternative approach in the repair of bone defects.展开更多
基金supported in part by National Natural Science Foundation of China(32271364 & 31971240)Interdisciplinary innovation project from West China Hospital of Stomatology, Sichuan University(RD-03-202305)。
文摘Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling. Here, we focused on the role of Semaphorin 3A(Sema3A), expressed by sensory nerves, in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement(OTM) model. Firstly, bone formation was activated after the 3rd day of OTM,coinciding with a decrease in sensory nerves and an increase in pain threshold. Sema3A, rather than nerve growth factor(NGF),highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM. Moreover, in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells(hPDLCs) within 24 hours.Furthermore, exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload. Mechanistically, Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway, maintaining mitochondrial dynamics as mitochondrial fusion. Therefore, Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation, both as a pain-sensitive analgesic and a positive regulator for bone formation.
基金supported by National Natural Science Foundation of China[31870961,81874027]Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions[312200102]+3 种基金Science&Technology Department of Sichuan Province[2020YFS0140,2021YFSY0003]Health Commission of Sichuan Province[19PJ104]Clinical Research Incubation project of West China Hospital of Sichuan University[2019HXFH041,2021HXFH036]the‘1.3.5 Program for Disciplines of Excellence’West China Hospital,Sichuan University。
文摘Cell-based tissue engineering is one of the optimistic approaches to replace current treatments for bone defects.Urine-derived stem cells(USCs)are obtained non-invasively and become one of the promising seed cells for bone regeneration.An injectable BMP2-releasing chitosan microspheres/type I collagen hydrogel(BMP2-CSM/Col I hydrogel)was fabricated.USCs proliferated in a time-dependent fashion,spread with good extension and interconnected with each other in different hydrogels both for 2D and 3D models.BMP2 was released in a sustained mode for more than 28 days.Sustained-released BMP2 increased the ALP activities and mineral depositions of USCs in 2D culture,and enhanced the expression of osteogenic genes and proteins in 3D culture.In vivo,the mixture of USCs and BMP2-CSM/Col I hydrogels effectively enhanced bone regeneration,and the ratio of new bone volume to total bone volume was 38%after 8weeks of implantation.Our results suggested that BMP2-CSM/Col I hydrogels promoted osteogenic differentiation of USCs in 2D and 3D culture in vitro and USCs provided a promising cell source for bone tissue engineering in vivo.As such,USCs-seeded hydrogel scaffolds are regarded as an alternative approach in the repair of bone defects.
