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Objective: Patients with rheumatoid arthritis (RA) are at increased risk for developing osteoporosis and fractures compared to controls.This risk is further increased since a majority of patients with RA also receive concomitant heal difficult when fracture.In addition, multiple factors lead to systemic osteoporosis.These conditions cause decreased bone mineral density and bone quality, and expose patients to an increased risk of fracture.Methods: To observe the fracture heal in RA model, after 15days the onset of arthritis a mid-shaft femur fracture model (RA+F group) was established (normal rats fracture model as control group NF group).Femurs were then harvested at 4 weeks, 8 weeks (n=5 per group) after fracture for micro-computed tomography (Micro-CT),X-Ray, histology test.In vitro study, BMSCs of fracture rat models were isolated, cultured and identified by flow cytometry analysis of CD45 and CD90.Then BMSCs were cultured in two cases, with or without TNF-α/IL-1 βstimulation.The Cell Counting Kit-8 (CCK-8) assay was performed to detect the proliferative activity.The osteogenic and chondrogenic properties of BMSCs in different environments are analyzed by alizarin red staining,alcian blue staning, alkaline phosphatase activity, osteocalcin secretion and gene expression of osteocalcin, collagen Ⅱ, collagen Ⅰ and aggrecan by qRT-PCR and WB assay.Results: The Micro CT images demonsrated the remodeling of the calcified callus, at 4 and 8 weeks after fracture, fracture gap could be clearly observed in RA+F group , while NF group better heal than RA+F group.NF group and the periosteal callus appeared to be homogenously filled with newly formed bone.X-Ray observed the results same as Micro-CT images.Fracture gap clearly observed in RA+F group.Sections obtained from the NF group after fracture showed more mature lamellar bone in the fracture gap, with more integrity, thick and continuous callus compared to RA+F group.In vitro study,BMSCs were CD90-CD45+ cells.Comparing with the BMSCs without stimulation, the proliferation of cells with TNF-α/IL-1β stimulation are slower, alizarin red staining after osteogenesis induction showed less calcium nodules and coloring shallow, gene expression and Western blot assay also showed that the osteogenic/chondrogenic capability of BMSCs with inflammatory stimulus were much weaker as well.Conclusion: The proliferative and osteogenic/chondrogenic capability of BMSCs in inflammatory environment decreased significantly, which revealed that the relative poor bone fracture healing of patients with chronic inflammatory disease like RA or bone tumor is closely related to the negative effects of inflammatory enviroment on BMSCs.In addition, multiple factors lead to systemic osteoporosis remarkably induced decrease in mineralized tissue and not well connected microstructure in newly formed callus, which may explain why RA patients has high risk of fracture and difficult heal when fracture.