Search

Summary Background/Objective Steroid-associated osteonecrosis (SAON) mostly occurs in large joints such as hip that finally results in joint collapse and replacement. An effective strategy for preventing SAON is inhibition of bone resorption and lipid formation, whereas promoting bone formation at osteonecrotic-sensitive skeletal sites. The objective of this study was to investigate whether gastrin administration could effectively prevent SAON in vivo and had a significant effect on osteogenesis, osteoclast differentiation and/or adipogenesis in vitro. Methods SAON was induced in rats by injection of both lipopolysaccharide and methylprednisolone. SAON rats were divided into three groups (untreated, low- ​and high-dose gastrin) and treated for two weeks. Lesions in SAON were identified, and efficacy of gastrin was evaluated in osteoclast activity, osteogenesis ​and adipogenesis. In vitro experiments evaluated the osteogenic and adipogenic potential of induced bone marrow stem cells, as well as osteoclast differentiation of stimulated bone marrow cells. Results Gastrin administration effectively prevented the development of SAON in vivo and significantly downregulated osteoclastogenesis, and upregulated osteogenesis in vitro. The underlying mechanism was potentially involved in the inhibited nuclear factor kappa-B (NF-κB) pathway leading to not only suppressed osteoclastogenesis but also facilitated osteoblastogenesis. Conclusion The present study demonstrated for the first time that gastrin could effectively prevent SAON in vivo and had a significant effect on osteogenesis, osteoclast differentiation and/or adipogenesis in vitro that should be an important link between gastrointestinal hormone and metabolic bone diseases. Translational potential of this article Gastrin prevents steroid-associated osteonecrosis with decreasing bone resorption and apoptosis, also enhancing bone formation. These findings provide in vivo evidence to support the use of gastrin to treat osteonecrosis.

Background/objectives For treatment of large bone defects challenging in orthopaedic clinics, bone graft substitutes are commonly used for the majority of surgeons. It would be proposed in the current study that our bioactive scaffolds could additionally serve as a local delivery system for therapeutic small molecule agents capable of providing support to enhance biological bone repair. Methods In this study, composite scaffolds made of poly (lactic-co-glycolic acid) (PLGA) and tricalcium phosphate (TCP) named by P/T was fabricated by a low-temperature rapid prototyping technique. For optimizing the scaffolds, the phytomolecule icaritin (ICT) was incorporated into P/T scaffolds called P/T/ICT. The osteogenic efficacies of the two groups of scaffolds were compared in a successfully established calvarial defect model in rats. Bone regeneration was evaluated by X-ray, micro-computerised tomography (micro-CT), and histology at weeks 4 and/or 8 post-implantation. In vitro induction of osteogenesis and osteoclastogenesis was established for identification of differentiation potentials evoked by icaritin in primary cultured precursor cells. Results The results of radiographies and decalcified histology demonstrated more area and volume fractions of newly formed bone within bone defect sites implanted with P/T/ICT scaffold than that with P/T scaffold. Undecalcified histological results presented more osteoid and mineralized bone tissues, and also more active bone remodeling in P/T/ICT group than that in P/T group. The results of histological staining in osteoclast-like cells and newly formed vessels indicated favorable biocompatibility, rapid bioresorption and more new vessel growth in P/T/ICT scaffolds in contrast to P/T scaffolds. Based on in vitro induction, the results presented that icaritin could significantly facilitate osteogenic differentiation, while suppressed adipogenic differentiation. Meanwhile, icaritin demonstrated remarkable inhibition of osteoclastogenic differentiation. Conclusion The finding that P/T/ICT composite scaffold can enhance bone regeneration in calvarial bone defects through facilitating effective bone formation and restraining excessive bone resorption. The translational potential of this article The osteogenic bioactivity of icaritin facilitated PLGA/TCP/icartin composite scaffold to exert significant bone regeneration in calvarial defects in rat model. It might form an optimized foundation for potential clinical validation in bone defects application.