IL-15 deficiency alleviates steroid-induced osteonecrosis of the femoral head by impact osteoclasts via RANKL-RANK-OPG system

Zubin Zhou,Xiaowei Yu,Nan Wang,Chenhao Pan,Yiwei Lin,Lihui Zhou,Youshui Gao,Haojie Shan

doi:10.1186/s12979-020-00190-0

Abstract

BackgroundWhether IL-15 is involved in the development of steroid-induced osteonecrosis of the femoral head (ONFH) is investigated.MethodsC57BL/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 unit-macrophage/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.ResultsIL-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.ConclusionIL-15 deficiency alleviates steroid-induced ONFH by impact osteoclasts via RANKL-RANK-OPG system.

Highlights

Osteonecrosis, called avascular necrosis, is the collapse of bone tissue due to lack of blood supply [1, 2] which commonly affects femur
Groups and treatment C57BL/6 J mice and Il15−/− mice were injected with methylprednisolone (21 mg/kg) subcutaneously for 4 consecutive weeks to set up steroid-induced ONFH groups as osteonecrosis WT group (WT ON) and osteonecrosis IL15−/− group (IL15−/− ON) as the previous report recommended [12], while C57BL/6 J mice and Il15−/− mice administrated with physiological saline were utilized as sham group and Il15−/− sham group
IL-15 contributes to the development of steroid-induced ONFH After steroid-induced ONFH model was established, IL15 level was detected

Summary

Introduction

Osteonecrosis, called avascular necrosis, is the collapse of bone tissue due to lack of blood supply [1, 2] which commonly affects femur. In consideration of the serious medical consequences and enormous economic costs incurred by ONFH, it is urgent and vital to find an effective option to improve bone repair and inhibit articulus collapse. Since the balance between osteoblasts and osteoclasts may play a vital role in bone formation, whether IL-15 deficiency may inhibit the development of steroid-induced ONFH is investigated. Whether IL-15 is involved in the development of steroid-induced osteonecrosis of the femoral head (ONFH) is investigated. 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.

Methods

Results

Conclusion