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

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 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. 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.

Identification of Candidate Genes Associated with Steroid-Induced Osteonecrosis of The Femoral Head by Bioinformatics Based on GEO Database

“…The previous studies have demonstrated that steroid is an established risk factor of osteonecrosis of the femoral head (ONFH) [4][5][6] . Moreover, numerous researches have proved that the mechanism of steroid-induced osteonecrosis of the femoral head (SONFH) including oxidative stress 7 , osteoclasts activation 8 , bone formation and resorption 9 , et al SONFH most have been diagnosed by magnetic resonance imaging (MRI) 5 . However, the reliable biomarkers of SONFH remained unknown.…”

Tanshinone I Mitigates Steroid-Induced Osteonecrosis of the Femoral Head and Activates the Nrf2 Signaling Pathway in Rats

“…However, long-term or excess application of glucocorticoids functions as an activator for inflammation. The elevation of proinflammatory cytokines has been found in a mouse model of SIONFH [ 10 , 31 ]. Similar results were found in the rat model of SIONFH in the current study.…”

ACP5, TNF, and MMP8 were identified as potential biomarkers of steroid-induced osteonecrosis of the femoral head

“…The etiology and pathological process of SONFH are complex. Oxidative stress [1] , osteoclasts activation [4] , and bone-metabolism disorder [5] have been correlated with SONFH. However, the exact molecular mechanisms of SONFH remain unclear.…”