Co-modification of calcium phosphate cement to achieve rapid bone regeneration in osteoporotic femoral condyle defect with lithium and aspirin.

Local application of lithium or aspirin with biological scaffold has been identified as a potent means to improve bone formation. In this study, lithium and aspirin modified calcium phosphate cement (Asp-Li/CPC) was prepared, and the feasibility of this biological scaffold in the treatment of osteoporotic bone defect was observed in vivo and in vitro. In vitro experiments confirmed that Asp-Li/CPC had better ability to promote MC3T3-E1 cells differentiation into osteoblasts, osteoblast mineralization and viability, and promote cell expression of ALP, OP, RUNX-2, OC and COL-1 protein than simple CPC or lithium modified CPC by MTT, Alizarin red staining and Western blot evaluation. In vivo experiments confirmed that Asp-Li/CPC presented the strongest effect on bone regeneration and bone mineralization through the comparison with CPC group and Li/CPC group with X-ray images, Micro-CT and Histological evaluation. RT-qPCR analysis showed that Asp-Li/CPC, Li/CPC group and CPC group demonstrated increased BMP2, Smad1, OPG than the OVX group (P<0.05), while Asp-Li/CPC exhibited decreased TNF-α, IFN-γ and RANKL than the OVX group (P<0.05). Experiments in vivo and in vitro show that Asp-Li/CPC is a scheme for rapid repair of femoral condylar defects, and these effects may be achieved by inhibiting local inflammation and through BMP-2/Smad1 and OPG/RANKL signaling pathway.

Rapamycin could increase the effects of melatonin against age-dependent bone loss.

Previous studies have demonstrated the beneficial effect of melatonin (MEL) on bone tissue and bone metabolism. Rapamycin (RAP) promotes osteoblast proliferation and inhibits osteoclast proliferation, and positively affects bone regeneration; however, reports about effects of RAP on bone loss for aged female rats with MEL administration are limited. This study investigated the impact of treatment with RAP on bone loss for aged female rats with MEL administration. Female Sprague-Dawley rats weighing approximately 520 g were randomly divided into 3 groups of 10: group CON, group MEL and group MEL + RAP and received saline, MEL, RAP plus MEL treatment until death at 12 weeks, respectively. The results of maintaining bone mass and bone strength with RAP plus MEL administration were evaluated by histology, microcomputerized tomography (Micro-CT), gene expression analysis and biomechanical testing. Results from this study indicated that MEL + RAP had stronger effects on the prevention and treatment of osteoporosis than MEL administration. Administration of MEL + RAP produced the strongest effects on bone parameters and strength for distal femurs and regulation of OPG/RANKL signalling pathway-related gene expression. These results seemed to indicate that RAP could increase the effects of MEL on age-dependent bone loss.