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

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

doi:10.1186/s12979-020-00190-0

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

Immun Ageing. 2020 Jun 12:17:19. doi: 10.1186/s12979-020-00190-0. eCollection 2020.

Authors

Zubin Zhou^#¹, Yiwei Lin^#¹, Chenhao Pan¹, Nan Wang², Lihui Zhou³, Haojie Shan¹, Youshui Gao¹, Xiaowei Yu¹

Affiliations

¹ Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233 China.
² Department of Emergency, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 Henan China.
³ Department of Orthopaedic Surgery, Xiangshan First People's Hospital, Ningbo, 315700 Zhejiang China.

^# Contributed equally.

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.

Keywords: IL-15; OPG; Osteonecrosis; RANK; RANKL.