Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory of Li Ka Shing Institute of Health, The Chinese University of Hong Kong, Hong Kong, PR China.; Pathology Center, Shanghai General Hospital/Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory of Li Ka Shing Institute of Health, The Chinese University of Hong Kong, Hong Kong, PR China.
Bone. 2018 Jan;106:52-60. doi: 10.1016/j.bone.2017.09.011. Epub 2017 Oct 10.
One of the effective strategies for prevention of steroid-associated osteonecrosis (SAON) is to inhibit bone resorption and fat formation and promote bone formation at osteonecrotic sensitive skeletal sites. We identified a novel phytomolecule that showed positive effects on osteogenesis, anti-bone resorption and anti-adipogenesis in vitro and also developed a bone-targeting delivery system (BTDS) for in vivo experimental study. The study investigated if our innovative synthesized BTDS carrying this phytomolecule would be able to effectively prevent SAON in a rat model. SAON was induced by combined injections of lipopolysaccharide and methylprednisolone. SAON rats were divided into four groups, one SAON untreated control group and three SAON treatment groups with different types of delivery systems (Asp-liposome-icaritin, liposome-icaritin and Asp-liposome) for two weeks. SAON lesions were identified and osteoclasts activity, osteogenesis and adipogenesis at these sites were evaluated by immunohistochemistry. Ex vitro study was also designed to evaluate the osteogenic and adipogenic potential of the isolated bone marrow stromal cells (BMSCs) via real-time PCR and histochemical staining. Our results showed that as a bone surface-specific BTDS, Asp-liposome-icaritin effectively prevented steroids-treated rats from SAON with significantly decreased osteocytes apoptosis, down-regulated osteoclatsogenesis and up-regulated osteogenesis. However, both liposome-icaritin and Asp-liposome treatment did not show significant efficacy for SAON prevention. In summary, this proof-concept-study showed for the first time that the innovative Asp-liposome-icaritin BTDS was effective for prevention of SAON in terms of bone resorption prevention, adipogenesis suppression, and bone-formation enhancement.
预防类固醇相关性骨坏死（SAON）的有效策略之一是抑制骨吸收和脂肪形成，并促进骨坏死敏感骨骼部位的骨形成。我们鉴定了一种新型植物分子，该分子在体外显示出促进成骨、抗骨吸收和抗脂肪形成的积极作用，并开发了一种用于体内实验研究的骨靶向递药系统（BTDS）。本研究探讨了我们创新合成的携带这种植物分子的 BTDS 是否能够有效预防大鼠模型中的 SAON。通过注射脂多糖和甲基强的松龙诱导 SAON。将 SAON 大鼠分为四组，一组为未治疗的 SAON 对照组和三组不同类型的递药系统（Asp-脂质体-icaritin、脂质体-icaritin 和 Asp-脂质体）治疗组，持续两周。通过免疫组织化学评估这些部位的 SAON 病变、破骨细胞活性、成骨和脂肪形成。还设计了离体研究，通过实时 PCR 和组织化学染色评估分离的骨髓基质细胞（BMSCs）的成骨和脂肪形成潜力。我们的结果表明，作为一种骨表面特异性 BTDS，Asp-脂质体-icaritin 可有效预防类固醇治疗的大鼠发生 SAON，显著降低成骨细胞凋亡、下调破骨细胞生成并上调成骨。然而，脂质体-icaritin 和 Asp-脂质体治疗均未显示出对 SAON 预防的显著疗效。总之，这项概念验证研究首次表明，创新的 Asp-脂质体-icaritin BTDS 在预防 SAON 方面是有效的，可预防骨吸收、抑制脂肪形成和增强骨形成。
