模拟失重通过抑制H型血管及血管-成骨耦联导致小鼠承重骨丢失OA

Objective To investigate the effects of simulated weightlessness on the morphology and function of H-type vessels in the weight-bearing bones of the mouse hindlimbs.Methods A simulated weightlessness model was established using the hindlimb unloading(HLU)method.Twelve 7-week-old male C57BL/6J mice were randomly divided into control group(CON group)and HLU group(n=6 per group),with HLU maintained for 21 d.After the experiment,the right tibia was scanned by MicroCT to evaluate bone morphological changes.The left tibia was fixed,decalcified,and sectioned for histological observation using HE staining,bone tissue immunohistochemistry,Goldner's trichrome staining,and immunofluorescence staining.RNA extracted from femoral tissues was analyzed by qRT-PCR to detect changes in gene expression.Results Compared with the CON group,the HLU group exhibited impaired tibial microstructure,reduced bone mass,and weakened new bone formation.mRNA expression of osteogenic differentiation-related molecules(Runx2,Osterix,Alp,and Osteocalcin)in the femur was significantly downregulated(P<0.01).A marked reduction in Ocn+osteoblasts was observed in the proximal tibial metaphysis.Concurrently,density of H-type vessels in tibial was significantly decreased(P<0.01),and mRNA expression of key angiogenesis-osteogenesis coupling mediators—HIF-1α,VEGFA,PDGF-BB,and TGF-β1—was also notably reduced(P<0.01).Conclusion Simulated weightlessness leads to concurrent bone loss and microvascular reduction in the mouse tibia,suggesting that H-type vessels may play a critical role in weightlessness induced decreases in weight-bearing bone mass.