We examined the effects of human umbilical cord-derived mesenchymal stem cells (HUMSCs) in Wharton's jelly on ovariectomy (OVX)-induced osteoporosis by using in vitro and in vivo experiments. Two months after OVX, the rats gained weight and had a decreased serum estradiol level . Both micro-computed tomography (micro-CT) and histochemical analyses revealed a marked decrease in the bone volume (BV) and collagen content within the head, neck, and distal condyle of the femur, indicating that the osteoporosis animal model was successfully established 2 mo after bilateral OVX. Subsequently, 2.5 × 10 HUMSCs were injected into the bone marrow cavity of the left femurs 2 mo after OVX. The rats were divided into the following groups: normal + phosphate-buffered saline (PBS), normal + HUMSCs, OVX + PBS, and OVX + HUMSCs. Two months after transplantation, both micro-CT imaging and histochemical staining revealed that the normal + HUMSCs group had higher BV and collagen content in the epiphysis and metaphysis than did the normal + PBS group. In the OVX + HUMSCs group, a substantial increase in the rod-shaped trabecular bone and the abundant accumulation of collagen were observed around the site of HUMSC transplantation. Plenty of transplanted HUMSCs remained viable and differentiated into osteoblasts. In addition, HUMSC transplantation reduced the number of osteoclasts. Compared with HUMSCs cultured alone, HUMSCs cocultured with osteoblasts showed that the percentage of cells differentiating into osteoblasts significantly increased. Furthermore, osteoclasts cocultured with HUMSCs had significantly decreased cellular activity and differentiation capability. HUMSC transplantation into the distal femur of OVX rats could locally stimulate osteocalcin synthesis, increase the trabecular bone, and inhibit osteoclast activity.
Introduction Focal bone destruction has a high prevalence in haemophilic arthropathy (HA) affected joints, but the mechanism remains unclear. Aim We undertook this study on clinic samples to explore the focal bone destruction in femoral heads suffered with end-stage HA. Methods Twenty-one femoral heads from HA patients and 19 femoral heads from rheumatoid arthritis (RA) patients were scanned by micro-CT. Histological analysis, including TRAP staining of subchondral bone were performed to evaluate the bone destruction and osteoclasts activity. RANKL, OPG as well as pro-inflammatory cytokines, such as TNF-α and IL-1β in subchondral bone were detected by immunohistochemistry (IHC) method. Results Severe focal lesion was observed in all the HA and RA femoral heads by micro-CT imaging and histological analysis. The mean percentage of lesion volume to total volume of the femoral heads from HA patients was significantly higher than those from RA patients. There was no significant difference in osteoclasts numbers in subchondral bone between HA and RA groups. By IHC analysis, high expression of RANKL, TNF-α, IL-1β and low expression of OPG and RANK were observed in subchondral bone, and there were no significant differences in the expression of RANKL, OPG, RANK, TNF-α and IL-1β in femoral heads derived from HA and RA patients. Conclusion Our findings demonstrated the focal bone destruction coupled with inflammatory osteoclastogenesis at subchondral bone in femoral heads from patients with end-stage HA, and that was similar to the changes in the femoral heads of RA patients.
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