IL-15 Deficiency Alleviates Steroid-induced Osteonecrosis of the Femoral Head by Impact Osteoclasts Via RANKL-RANK-OPG System

Overview

Journal Immun Ageing

Publisher Biomed Central

Specialty Geriatrics

Date 2020 Jun 16

PMID 32536957

Citations 9

Authors

Zubin Zhou

Yiwei Lin

Chenhao Pan

Nan Wang

Lihui Zhou

Haojie Shan

Youshui Gao

Xiaowei Yu

Affiliations

Soon will be listed here.

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 l15mice 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.

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References

Djaafar S, Pierroz D, Chicheportiche R, Zheng X, Ferrari S, Ferrari-Lacraz S . Inhibition of T cell-dependent and RANKL-dependent osteoclastogenic processes associated with high levels of bone mass in interleukin-15 receptor-deficient mice. Arthritis Rheum. 2010; 62(11):3300-10. DOI: 10.1002/art.27645. View

Ranefall P, Wester K, Busch C, Malmstrom P, Bengtsson E . Automatic quantification of microvessels using unsupervised image analysis. Anal Cell Pathol. 1999; 17(2):83-92. PMC: 4611099. DOI: 10.1155/1998/490585. View

Mbalaviele G, Jaiswal N, Meng A, Cheng L, van den Bos C, Thiede M . Human mesenchymal stem cells promote human osteoclast differentiation from CD34+ bone marrow hematopoietic progenitors. Endocrinology. 1999; 140(8):3736-43. DOI: 10.1210/endo.140.8.6880. View

Bergmann B, Jirholt P, Henning P, Lindholm C, Ohlsson C, McInnes I . Antibiotics with Interleukin-15 Inhibition Reduce Joint Inflammation and Bone Erosions but Not Cartilage Destruction in Staphylococcus aureus-Induced Arthritis. Infect Immun. 2018; 86(5). PMC: 5913847. DOI: 10.1128/IAI.00960-17. View

Koh J, Oh B, Ha M, Cho K, Lee J, Park B . Association of IL-15 polymorphisms with bone mineral density in postmenopausal Korean women. Calcif Tissue Int. 2009; 85(5):369-78. DOI: 10.1007/s00223-009-9290-2. View

Bai Y, Yang F, Xuan K, Bai Y, Wu B . Inhibition of RANK/RANKL signal transduction pathway: a promising approach for osteoporosis treatment. Med Hypotheses. 2008; 71(2):256-8. DOI: 10.1016/j.mehy.2008.03.021. View

Zhao R, Wang H, Wang X, Feng F . Steroid therapy and the risk of osteonecrosis in SARS patients: a dose-response meta-analysis. Osteoporos Int. 2016; 28(3):1027-1034. PMC: 7079838. DOI: 10.1007/s00198-016-3824-z. View

Ogata Y, Kukita A, Kukita T, Komine M, Miyahara A, Miyazaki S . A novel role of IL-15 in the development of osteoclasts: inability to replace its activity with IL-2. J Immunol. 1999; 162(5):2754-60. View

Cui L, Zhuang Q, Lin J, Jin J, Zhang K, Cao L . Multicentric epidemiologic study on six thousand three hundred and ninety five cases of femoral head osteonecrosis in China. Int Orthop. 2015; 40(2):267-76. DOI: 10.1007/s00264-015-3061-7. View

10.

Bezerra M, Carvalho J, Prokopowitsch A, Pereira R . RANK, RANKL and osteoprotegerin in arthritic bone loss. Braz J Med Biol Res. 2005; 38(2):161-70. DOI: 10.1590/s0100-879x2005000200004. View

11.

Soderstrom K, Stein E, Colmenero P, Purath U, Muller-Ladner U, de Matos C . Natural killer cells trigger osteoclastogenesis and bone destruction in arthritis. Proc Natl Acad Sci U S A. 2010; 107(29):13028-33. PMC: 2919936. DOI: 10.1073/pnas.1000546107. View

12.

Mont M, Pivec R, Banerjee S, Issa K, Elmallah R, Jones L . High-Dose Corticosteroid Use and Risk of Hip Osteonecrosis: Meta-Analysis and Systematic Literature Review. J Arthroplasty. 2015; 30(9):1506-1512.e5. PMC: 7127809. DOI: 10.1016/j.arth.2015.03.036. View

13.

Papadopouli A, Klonaris C, Theocharis S . Role of OPG/RANKL/RANK axis on the vasculature. Histol Histopathol. 2008; 23(4):497-506. DOI: 10.14670/HH-23.497. View

14.

Zhang N, Li Z, Wei H, Liu Z, Hernigou P . Steroid-induced osteonecrosis: the number of lesions is related to the dosage. J Bone Joint Surg Br. 2008; 90(9):1239-43. DOI: 10.1302/0301-620X.90B9.20056. View

15.

Ikeuchi K, Hasegawa Y, Seki T, Takegami Y, Amano T, Ishiguro N . Epidemiology of nontraumatic osteonecrosis of the femoral head in Japan. Mod Rheumatol. 2014; 25(2):278-81. DOI: 10.3109/14397595.2014.932038. View

16.

Feng S, Madsen S, Viller N, Neutzsky-Wulff A, Geisler C, Karlsson L . Interleukin-15-activated natural killer cells kill autologous osteoclasts via LFA-1, DNAM-1 and TRAIL, and inhibit osteoclast-mediated bone erosion in vitro. Immunology. 2015; 145(3):367-79. PMC: 4479536. DOI: 10.1111/imm.12449. View

17.

Eriksen E, Mosekilde L, Melsen F . Trabecular bone remodeling and bone balance in hyperthyroidism. Bone. 1985; 6(6):421-8. DOI: 10.1016/8756-3282(85)90218-2. View

18.

Geusens P . The role of RANK ligand/osteoprotegerin in rheumatoid arthritis. Ther Adv Musculoskelet Dis. 2012; 4(4):225-33. PMC: 3403250. DOI: 10.1177/1759720X12438080. View

19.

Tian L, Baek S, Jang J, Kim S . Imbalanced bone turnover markers and low bone mineral density in patients with osteonecrosis of the femoral head. Int Orthop. 2018; 42(7):1545-1549. DOI: 10.1007/s00264-018-3902-2. View

20.

Zhang Q, L V J, Jin L . Role of coagulopathy in glucocorticoid-induced osteonecrosis of the femoral head. J Int Med Res. 2017; 46(6):2141-2148. PMC: 6023042. DOI: 10.1177/0300060517700299. View