title: Src siRNA prevents corticosteroid-associated osteoporosis in a rabbit model.
abstract: In an established steroid-associated osteonecrosis (SAON) rabbit model we found recently that blockage Src by siRNA could improve reconstructive repair of osteonecrosis via enhancing osteogenesis and inhibiting bone resorption. The current study investigated if blocking Src was able to prevent steroid-associated osteoporosis (SAOP) in the same SAON animal model. Rabbits were treated with pulsed lipopolysaccharide (LPS) and corticosteroid methylprednisolone (MPS). At 2, 4, and 6weeks after induction, Src siRNA, control siRNA and saline were intramedullary injected into proximal femur, respectively. Two fluorescent dyes xylenol orange and calcein green were injected before sacrificing the animals for in vivo labeling of the newly formed bone. At week 6 after induction, proximal femora of rabbits were dissected for micro-CT and histological analysis. Results showed significant bone loss in the metaphysis of femoral head in the control rabbits after SAON induction. Src siRNA treatment was able to prevent steroid-associate bone loss in trabecular bone and increase cortical bone thickness at femoral neck. Histomorphometry showed that Src siRNA increased the osteoblastic bone formation and decreased the eroded bone surfaces suggesting decreased osteoclastic bone resorption. This was the first study to report bone loss after SAON induction in rabbit model that could be prevented by knocking down Src by siRNA.
authors.affiliation: Musculoskeletal Research Laboratory, Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Li-Zhen
authors.initials: LZ
authors.lastname: Zheng
authors.affiliation: Musculoskeletal Research Laboratory, Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong, China; Translational Medicine R&D Center, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, PR China.
authors.forename: Xin-Luan
authors.initials: XL
authors.lastname: Wang
authors.affiliation: Translational Medicine R&D Center, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, PR China.
authors.forename: Hui-Juan
authors.initials: HJ
authors.lastname: Cao
authors.affiliation: Musculoskeletal Research Laboratory, Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Shi-Hui
authors.initials: SH
authors.lastname: Chen
authors.affiliation: Musculoskeletal Research Laboratory, Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Le
authors.initials: L
authors.lastname: Huang
authors.affiliation: Musculoskeletal Research Laboratory, Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong, China; Translational Medicine R&D Center, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, PR China. Electronic address: lingqin@cuhk.edu.hk.
authors.forename: Ling
authors.initials: L
authors.lastname: Qin
mesh_terms: D000305:Adrenal Cortex Hormones / Q000009:adverse effects*; D000818:Animals; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000473:pathology; D002113:Calcification, Physiologic; D004195:Disease Models, Animal; D020868:Gene Silencing; D008297:Male; D010024:Osteoporosis / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000517:prevention & control*; D034741:RNA, Small Interfering / Q000627:therapeutic use*; D011817:Rabbits; D060888:Real-Time Polymerase Chain Reaction; D055114:X-Ray Microtomography; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D000305:Adrenal Cortex Hormones; D034741:RNA, Small Interfering; D019061:src-Family Kinases
keywords: Corticosteroid; Osteoporosis; Src; siRNA