A novel bone targeting delivery system carrying phytomolecule icaritin for prevention of steroid-associated osteonecrosis in rats

Shihui Chen, Lizhen Zheng, Jiayong Zhang, Heng Wu, Nan Wang, Wenxue Tong, Jiankun Xu, Le Huang, Yifeng Zhang, Zhijun YANG, Ge Lin, Xinluan Wang*, Ling Qin

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)52-60
Number of pages9
JournalBone
Volume106
DOIs
Publication statusPublished - Jan 2018

Scopus Subject Areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

User-Defined Keywords

  • Anti-resorption
  • Bioengineering
  • Bone histomorphometry
  • Corticosteroids
  • Osteonecrosis

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