Abstract:Objective: To investigate the effect of human umbilical cord mesenchymal stem cells (HUC-MSCs) on osteoporosis rats and its mechanism. Methods: Thirty SPF grade 6-month-old female rats were randomly divided into three groups: sham operation group (Sham group), ovariectomy group (OVX group) and HUC-MSCs intervention group (HUC-MSCs group) (4×106/3 day), with 10 rats in each group. In Sham group, a small amount of abdominal fat was removed, and the other groups were removed bilateral ovaries to establish osteoporosis rat model. After successful modeling, HUC-MSCs group was intervened with stem cells for 12 w, while the other two groups were intervened with equal dose of normal saline. After the intervention, calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), c-terminal peptide of type I collagen (CTX), histomorphometric parameters of femur, bone mineral density (BMD), osteoblast surface/bone surface ratio (ObS/BS) and osteoclast surface area/bone surface (OcS/BS) were used to evaluate the improvement of osteoporosis in rats. Meanwhile, the expression of osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL), β-catenin and Runt-related transcription factor 2 (Runx2) were detected by Western blot. Results: The contents of serum Ca and ALP in HUC-MSCs group were significantly higher than those in OVX group (2.320±0.188 vs.1.822±0.139; 79.584±8.349 vs.43.644±5.369; all P=0.000) ; P and CTX contents were significantly lower than those in OVX group (1.651±0.068 vs.1.864±0.076, P=0.000; 119.832±18.180 vs.144.272±15.629, P=0.039) ; BMD, the number of trabecular bone, the ratio of trabecular area and ObS/BS in HUC-MSCs group were significantly higher than those in OVX group (161.114±16.726 vs.126.558±7.100, P=0.009; 1.702±0.220 vs.1.051±0.323, P=0.020; 33.111±6.101 vs.19.575±5.629, P=0.022; 45.279±3.947 vs.33.948±7.339, P=0.041) ; the bone trabecular separation and OcS/BS in HUC-MSCs group were significantly lower than those in OVX group (0.592±0.066 vs.0.845±0.165, P=0.018; 37.532±3.910 vs.44.891±3.615, P=0.026) ; the results of Western blot showed that the ratio of OPG/RANKL and the protein expression of β-catenin and Runx2 in HUC-MSCs group were significantly higher than those in OVX group (0.776±0.045 vs.0.097±0.063, P=0.000; 0.590±0.057 vs.0.202±0.088, P=0.000; 0.595±0.078 vs.0.239±0.071, P=0.001) . Conclusion: HUC-MSCs can regulate OPG/RANKL ratio through Wnt/β-catenin/Runx2 pathway, thus promoting bone formation, inhibiting bone resorption and improving osteoporosis.
