Abstract
BackgroundOsteoporosis is a metabolic bone disorder characterized by deterioration in the quantity and quality of bone tissue, with a consequent increase susceptibility to fracture.MethodsIn this study, we sought to determine the efficacy of platelet-rich fibrin releasates (PRFr) in augmenting the therapeutic effects of stem cell-based therapy in treating osteoporotic bone disorder. An osteoporosis mouse model was established through bilateral ovariectomy on 12-week-old female ICR (Institute of Cancer Research) mice. Eight weeks postoperatively, the ovariectomized (OVX) mice were left untreated (control) or injected with PRFr, bone marrow stem cells (BMSCs), or the combination of BMSCs and PRFr. Two different injection (single versus quadruple) dosages were tested to investigate the accumulative effects of BMSCS and PRFr on bone quality.Eight weeks after injection, the changes in tibial microstructural profiles included the percentage of bone volume versus total tissue volume (BV/TV, %), bone mineral density (BMD, g/cm3), trabecular number (Tb.N, number/mm), and trabecular separation (Tb.Sp, mm) and bony histology were analyzed.ResultsPostmenopausal osteoporosis model was successfully established in OVX mice, evidenced by reduced BMD, decreased BV/TV, lower Tb.N but increased Tb.Sp. Eight weeks after injection, there was no significant change to BMD and bone trabeculae could be detected in mice that received single-injection regimen. In contrast, in mice which received 4 doses of combined PRFr and BMSCs, the BMD, BV/TV, and TB.N increased, and the TB.Sp decreased significantly compared to untreated OVX mice. Moreover, the histological analysis showed the trabecular spacing become narrower in OVX-mice treated with quadruple injection of BMSCs and combined PRFr and BMSCs than untreated control.ConclusionThe systemic administration of combined BMSCs and PRFr protected against OVX-induced bone mass loss in mice. Moreover, the improvement of bony profile scores in quadruple-injection group is better than the single-injection group, probably through the increase in effect size of cells and growth factors. Our data also revealed the combination therapy of BMSCs and PRFr has better effect in enhancing osteogenesis, which may provide insight for the development of a novel therapeutic strategy in osteoporosis treatment.
Highlights
Osteoporosis is a metabolic bone disorder characterized by deterioration in the quantity and quality of bone tissue, with a consequent increase susceptibility to fracture
The systemic administration of combined bone marrow stem cells (BMSC) and platelet-rich fibrin (PRF) releasates (PRFr) protected against OVX-induced bone mass loss in mice
A phenotype of CD44+ CD90+ CD34− CD45− cell surface markers was identified in the passage 2 (P2) BMSCs
Summary
Osteoporosis is a metabolic bone disorder characterized by deterioration in the quantity and quality of bone tissue, with a consequent increase susceptibility to fracture. An increased risk of fractures, in particular hip, spine, and wrist would occur in osteoporotic patients who sustained low energy injury [2]. Throughout life, bones are in dynamic equilibrium, meaning that they are continuously remodeled by osteoclast-mediated bone resorption and osteoblast-mediated bone formation [3]. The disruption of equilibrium of bone remodeling would happen when the bone-forming osteoblasts activity is surpassed by osteoclast-mediated bone resorption thereby contributes to the pathogenesis in osteoporosis [4,5,6,7]. Current evidences have shown encouraging results of both types of drugs in improving BMD and reducing fracture risk, there are growing concerns about devastating drug-related complications such as osteonecrosis of jaw and atypical femoral fractures [10,11,12]
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