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A novel bone targeting delivery system carrying phytomolecule icaritin for prevention of steroid-associated
Shihui Chen1, Lizhen Zheng2, Jiayong Zhang3
1Musculoskeletal 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.
Abstract:
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 (Asp8-liposome-icaritin, liposome-icaritin and Asp8-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, Asp8-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 Asp8-liposome treatment did not show significant efficacy for SAON prevention. In summary, this proof-concept-study showed for the first time that the innovative Asp8-liposome-icaritin BTDS was effective for prevention of SAON in terms of bone resorption prevention, adipogenesis suppression, and bone-formation enhancement.
Insights
A novel bone-targeting delivery system (BTDS) carrying a phytomolecule effectively prevented steroid-associated osteonecrosis (SAON) in rats. This innovative Asp8-liposome-icaritin BTDS enhanced bone formation and reduced bone resorption and fat formation.
Area of Science:
- Biomedical Engineering
- Orthopedics
- Pharmacology
Background:
- Steroid-associated osteonecrosis (SAON) is a debilitating condition requiring effective prevention strategies.
- Current strategies aim to inhibit bone resorption and fat formation while promoting bone formation at susceptible skeletal sites.
Purpose of the Study:
- To investigate the efficacy of a novel bone-targeting delivery system (BTDS) carrying a phytomolecule for preventing SAON.
- To evaluate the effects of Asp8-liposome-icaritin on osteogenesis, bone resorption, and adipogenesis in a rat model of SAON.
Main Methods:
- SAON was induced in rats using combined lipopolysaccharide and methylprednisolone injections.
- Treatment groups received different delivery systems, including Asp8-liposome-icaritin, liposome-icaritin, and Asp8-liposome, for two weeks.
- SAON lesions, osteoclast activity, osteogenesis, and adipogenesis were assessed using immunohistochemistry and ex vivo cell studies.
Main Results:
- Asp8-liposome-icaritin significantly prevented SAON by decreasing osteocyte apoptosis, down-regulating osteoclastogenesis, and up-regulating osteogenesis.
- Control treatments (liposome-icaritin and Asp8-liposome) did not show significant efficacy in SAON prevention.
- Ex vivo studies confirmed the osteogenic and adipogenic potential of isolated bone marrow stromal cells.
Conclusions:
- The novel Asp8-liposome-icaritin BTDS is a promising strategy for SAON prevention.
- This bone-targeting delivery system effectively inhibits bone resorption, suppresses adipogenesis, and enhances bone formation.
- This study provides a proof-of-concept for an innovative approach to combatting steroid-associated osteonecrosis.