IL-15 deficiency alleviates steroid-induced osteonecrosis of the femoral head by impact osteoclasts via RANKL-RANK-OPG s
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RESEARCH
Open Access
IL-15 deficiency alleviates steroid-induced osteonecrosis of the femoral head by impact osteoclasts via RANKL-RANK-OPG system Zubin Zhou1†, Yiwei Lin1†, Chenhao Pan1, Nan Wang2, Lihui Zhou3, Haojie Shan1, Youshui Gao1 and Xiaowei Yu1*
Abstract Background: Whether IL-15 is involved in the development of steroid-induced osteonecrosis of the femoral head (ONFH) is investigated. Methods: C57BL/6 J and l15−/−mice were injected with methylprednisolone to induce wide type osteonecrosis (WT ON) and IL-15 deficiency osteonecrosis (IL-15−/− ON). Hematoxylin-Eosin (H&E) staining and micro-computed tomography (micro-CT) scanning was used to detect the microstructure. The differentiation and formation of osteoclasts were determined with colony-forming unit-granulocyte macrophages (CFU-GM), colony-forming unitmacrophage/mononuclear (CFU-M) per tibia, and tartrate-resistant acid phosphatase (TRACP or TRAP) positive cells. Serum interleukin (IL)-15, osteocalcin, bone alkaline phosphatase (BAP), bone Gla protein (BGP), and TRACP were assayed with enzyme-linked immunosorbent assay (ELISA). The receptor activator of nuclear factor-κB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) in the femoral heads were detected by Western blot. CD34 staining was performed to detect microvascular density. Results: IL-15 secretion was increased in the femoral heads and the serum of steroid-induced ONFH mice. IL-15 deficiency may lead to up-regulated vessel remodeling, improved microstructure, and up-regulated serum osteocalcin, BAP, and BGP secretion. Both the expression of RANKL/RANK/OPG and osteoclast differentiation and formation can be down-regulated by IL-15 deficiency. Conclusion: IL-15 deficiency alleviates steroid-induced ONFH by impact osteoclasts via RANKL-RANK-OPG system. Keywords: IL-15, Osteonecrosis, RANKL, RANK, OPG
Introduction Osteonecrosis, also called avascular necrosis, is the collapse of bone tissue due to lack of blood supply [1, 2] which commonly affects femur. Although osteonecrosis can happen without any apparent reason, high-dose * Correspondence: [email protected] † Zubin Zhou and Yiwei Lin contributed equally to this work. 1 Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China Full list of author information is available at the end of the article
usage of glucocorticoids (steroid hormones), alcoholism, bone fractures, and joint dislocations are considered to be the risk factors. At present medical practice, the steroid is indispensably utilized to treat various diseases, such as nephrotic syndrome, renal transplantation, acute lymphoblastic leukemia, rheumatoid arthritis, and systemic lupus erythematosus, which will be accompanied with the serious complication of steroid-induced osteonecrosis of the femoral head (ONFH) and hip
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