IL-34 Aggravates Steroid-Induced Osteonecrosis of the Femoral Head via Promoting Osteoclast Differentiation
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
IL-34 can promote osteoclast differentiation and activation, which may contribute to steroid-induced osteonecrosis of the femoral head (ONFH). Animal model was constructed in both BALB/c and IL-34 deficient mice to detect the relative expression of inflammation cytokines. Micro-CT was utilized to reveal the internal structure. In vitro differentiated osteoclast was induced by culturing bone marrow-derived macrophages with IL-34 conditioned medium or M-CSF. The relative expression of pro-inflammation cytokines, osteoclast marker genes, and relevant pathways molecules was detected with quantitative real-time RT-PCR, ELISA, and Western blot. Up-regulated IL-34 expression could be detected in the serum of ONFH patients and femoral heads of ONFH mice. IL-34 deficient mice showed the resistance to ONFH induction with the up-regulated trabecular number, trabecular thickness, bone value fraction, and down-regulated trabecular separation. On the other hand, inflammatory cytokines, such as TNF-α, IFN-γ, IL-6, IL-12, IL-2, and IL-17A, showed diminished expression in IL-34 deficient ONFH induced mice. IL-34 alone or works in coordination with M-CSF to promote osteoclastogenesis and activate ERK, STAT3, and non-canonical NF-κB pathways. These data demonstrate that IL-34 can promote the differentiation of osteoclast through ERK, STAT3, and non-canonical NF-κB pathways to aggravate steroid-induced ONFH, and IL-34 can be considered as a treatment target.
Abstract
IL-34 can promote osteoclast differentiation and activation, which may contribute to steroid-induced osteonecrosis of the femoral head (ONFH). Animal model was constructed in both BALB/c and IL-34 deficient mice to detect the relative expression of inflammation cytokines. Micro-CT was utilized to reveal the internal structure. In vitro differentiated osteoclast was induced by culturing bone marrow-derived macrophages with IL-34 conditioned medium or M-CSF. The relative expression of pro-inflammation cytokines, osteoclast marker genes, and relevant pathways molecules was detected with quantitative real-time RT-PCR, ELISA, and Western blot. Up-regulated IL-34 expression could be detected in the serum of ONFH patients and femoral heads of ONFH mice. IL-34 deficient mice showed the resistance to ONFH induction with the up-regulated trabecular number, trabecular thickness, bone value fraction, and down-regulated trabecular separation. On the other hand, inflammatory cytokines, such as TNF-α, IFN-γ, IL-6, IL-12, IL-2, and IL-17A, showed diminished expression in IL-34 deficient ONFH induced mice. IL-34 alone or works in coordination with M-CSF to promote osteoclastogenesis and activate ERK, STAT3, and non-canonical NF-κB pathways. These data demonstrate that IL-34 can promote the differentiation of osteoclast through ERK, STAT3, and non-canonical NF-κB pathways to aggravate steroid-induced ONFH, and IL-34 can be considered as a treatment target.
참고문헌 (31)
- Chang C, "The pathogenesis, diagnosis and clinical manifestations of steroid-induced osteonecrosis", J Autoimmun, 110, pp.102460~ (2020)
- Krez A, "Risk factors for multi-joint disease in patients with glucocorticoid-induced osteonecrosis", Osteoporos Int, 32, pp.2095~2103 (2021)
- Musso ES, "Results of conservative management of osteonecrosis of the femoral head. A retrospective review", Clin Orthop Relat Res, pp.209~215 (1986)
- Chen K, "Steroid-induced osteonecrosis of the femoral head reveals enhanced reactive oxygen species and hyperactive osteoclasts", Int J Biol Sci, 16, pp.1888~1900 (2020)
- Guggenbuhl P, "Etiology of avascular osteonecrosis of the femoral head", Morphologie, 105, pp.80~84 (2021)
- Yoon BH, "The 2019 revised version of association research circulation osseous staging system of osteonecrosis of the femoral head", J Arthroplasty, 35, pp.933~940 (2020)
- Wen Z, "Influence of cigarette smoking on osteonecrosis of the femoral head(ONFH) : a systematic review and meta-analysis", Hip Int, 27, pp.425~435 (2017)
- Wang A, "The pathogenesis of steroid-induced osteonecrosis of the femoral head : a systematic review of the literature", Gene, 671, pp.103~109 (2018)
- Okazaki S, "High risk of osteonecrosis of the femoral head in autoimmune disease patients showing no immediate increase in hepatic enzyme under steroid therapy", Rheumatol Int, 33, pp.51~55 (2013)
- Zhao R, "Steroid therapy and the risk of osteonecrosis in SARS patients : a dose-response meta-analysis", Osteoporos Int, 28, pp.1027~1034 (2017)
- Wang M, "Bone morphogenetic protein 2 controls steroid-induced osteonecrosis of the femoral head via directly inhibiting interleukin-34 expression", J Mol Endocrinol, 68, pp.1~9 (2021)
- Luo P, "The role of autophagy in steroid necrosis of the femoral head : a comprehensive research review", Int Orthop, 42, pp.1747~1753 (2018)
- Fu D, "Proper mechanical stress promotes femoral head recovery from steroid-induced osteonecrosis in rats through the OPG", RANK, BMC Musculoskelet Disord, pp.2020, 21[DOI]
- Petek D, "Osteonecrosis of the femoral head : pathophysiology and current concepts of treatment", EFORT Open Rev, 4, pp.85~97 (2019)
- He MC, "Osteoclastic activity was associated with the development of steroid-induced osteonecrosis of femoral head", Artif Cells Nanomed Biotechnol, 48, pp.1036~1046 (2020)
- Baghdadi M, "A role for IL-34 in osteolytic disease of multiple myeloma", Blood Adv, 3, pp.541~551 (2019)
- Poudel M, "Interleukin-34-csf1r signaling axis promotes epithelial cell transformation and breast tumorigenesis", Int J Mol Sci, 22, pp.2711~ (2021)
- Zou D, "Th17 and IL-17 exhibit higher levels in osteonecrosis of the femoral head and have a positive correlation with severity of pain", Endokrynol Pol, 69, pp.283~290 (2018)
- Zheng Y, "Osteonecrosis in systemic lupus erythematosus : Systematic insight from the epidemiology, pathogenesis, diagnosis and management", Autoimmun Rev, 21, pp.102992~ (2022)
- Liu Y, "IKKe in osteoclast inhibits the progression of methylprednisolone-induced osteonecrosis", Int J Biol Sci, 17, pp.1353~1360 (2021)
- Wang J, "Nik inhibitor impairs chronic periodontitis via suppressing non-canonical NF-κB and osteoclastogenesis", Pathog Dis, 78, pp.ftaa045~ (2020)
- Freuchet A, "IL-34 and CSF-1, deciphering similarities and differences at steady state and in diseases", J Leukoc Biol, 110, pp.771~796 (2021)
- Foucher ED, "IL-34-and M-CSF-induced macrophages switch memory T cells into Th17 cells via membrane IL-1α", Eur J Immunol, 45, pp.1092~1102 (2015)
- Ge Y, "Biological functions and clinical implications of interleukin-34 in inflammatory diseases", Adv Protein Chem Struct Biol, 119, pp.39~63 (2020)
- Lin H, "Discovery of a cytokine and its receptor by functional screening of the extracellular proteome", Science, 320, pp.807~811 (2008)
- Muñoz-Garcia J, "The twin cytokines interleukin-34 and CSF-1 : masterful conductors of macrophage homeostasis", Theranostics, 11, pp.1568~1593 (2021)
- Lelios I, "Emerging roles of IL-34 in health and disease", J Exp Med, 217, pp.e20190290~ (2020)
- 문세환, "The M-CSF receptor in osteoclasts and beyond", Experimental and Molecular Medicine, 52, pp.1~16 (2020), 생화학분자생물학회[DOI]
- Stanley ER, "CSF-1 receptor signaling in myeloid cells", Cold Spring Harb Perspect Biol, 6, pp.a021857~ (2014)
- Li X, "Effect of IL-34 on T helper 17 cell proliferation and IL-17 secretion by peripheral blood mononuclear cells from rheumatoid arthritis patients", Sci Rep, 10, pp.22239~ (2020)
- Baghdadi M, "Interleukin 34, from pathogenesis to clinical applications", Cytokine, 99, pp.139~147 (2017)