Interferon–JAK–STAT Axis in Bone Metabolism

Wada T, Nakashima T, Hiroshi N, Penninger JM. RANKL-RANK signaling in osteoclastogenesis and bone disease. Trends Mol Med. 2006;12(1):17–25.

Article  CAS  PubMed  Google Scholar 

Teitelbaum SL. Bone resorption by osteoclasts. Science. 2000;289(5484):1504–8.

Article  CAS  PubMed  Google Scholar 

Karsenty G, Kronenberg HM, Settembre C. Genetic control of bone formation. Annu Rev Cell Dev Biol. 2009;25:629–48.

Article  CAS  PubMed  Google Scholar 

Yadav S, Yadav J, Jones D, Humphrey MB. Osteoimmunology: the little niche with the big impact. Am J Med Sci. 2025.

Tang M, Tian L, Luo G, Yu X. Interferon-gamma-mediated osteoimmunology. Front Immunol. 2018;9:1508.

Article  PubMed  PubMed Central  Google Scholar 

Li S, Liu G, Hu S. Osteoporosis: interferon-gamma-mediated bone remodeling in osteoimmunology. Front Immunol. 2024;15:1396122.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhao Z, Du Y, Yan K, Zhang L, Guo Q. Exercise and osteoimmunology in bone remodeling. FASEB J. 2024;38(7):e23554.

Article  CAS  PubMed  Google Scholar 

Deng Z, Hu W, Ai H, Chen Y, Dong S. The dramatic role of IFN family in aberrant inflammatory osteolysis. Curr Gene Ther. 2021;21(2):112–29.

Article  CAS  PubMed  Google Scholar 

Place DE, Malireddi RKS, Kim J, Vogel P, Yamamoto M, Kanneganti TD. Osteoclast fusion and bone loss are restricted by interferon inducible guanylate binding proteins. Nat Commun. 2021;12(1):496.

Article  CAS  PubMed  PubMed Central  Google Scholar 

MacLauchlan S, Kushwaha P, Tai A, Chen S, Manning C, Swarnkar G, et al. Sting-dependent interferon signatures restrict osteoclast differentiation and bone loss in mice. Proc Natl Acad Sci U S A. 2023;120(15):e2210409120.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gao Y, Grassi F, Ryan MR, Terauchi M, Page K, Yang X, et al. IFN-gamma stimulates osteoclast formation and bone loss in vivo via antigen-driven T cell activation. J Clin Invest. 2007;117(1):122–32.

Article  CAS  PubMed  Google Scholar 

Duque G, Huang DC, Dion N, Macoritto M, Rivas D, Li W, et al. Interferon-γ plays a role in bone formation in vivo and rescues osteoporosis in ovariectomized mice. J Bone Miner Res. 2011;26(7):1472–83.

Article  CAS  PubMed  Google Scholar 

Takayanagi H, Kim S, Taniguchi T. Signaling crosstalk between RANKL and interferons in osteoclast differentiation. Arthritis Res. 2002;4(3):S227-32.

Article  PubMed  PubMed Central  Google Scholar 

Yim HY, Park C, Lee YD, Arimoto K, Jeon R, Baek SH, et al. Elevated response to type I IFN enhances RANKL-mediated osteoclastogenesis in Usp18-knockout mice. J Immunol. 2016;196(9):3887–95.

Article  CAS  PubMed  Google Scholar 

Kohara H, Kitaura H, Fujimura Y, Yoshimatsu M, Morita Y, Eguchi T, et al. IFN-γ directly inhibits TNF-α-induced osteoclastogenesis in vitro and in vivo and induces apoptosis mediated by Fas/Fas ligand interactions. Immunol Lett. 2011;137(1–2):53–61.

Article  CAS  PubMed  Google Scholar 

Chen Y, Wang Y, Tang R, Yang J, Dou C, Dong Y, et al. Dendritic cells-derived interferon-λ1 ameliorated inflammatory bone destruction through inhibiting osteoclastogenesis. Cell Death Dis. 2020;11(6):414.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Peng Q, Luo A, Zhou Z, Xuan W, Qiu M, Wu Q, et al. Interleukin 29 inhibits RANKL-induced osteoclastogenesis via activation of JNK and STAT, and inhibition of NF-κB and NFATc1. Cytokine. 2019;113:144–54.

Article  CAS  PubMed  Google Scholar 

Xu J, Wang Y, Li J, Zhang X, Geng Y, Huang Y, et al. IL-12p40 impairs mesenchymal stem cell-mediated bone regeneration via CD4(+) T cells. Cell Death Differ. 2016;23(12):1941–51.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Liu CJ, Chang E, Yu J, Carlson CS, Prazak L, Yu XP, et al. The interferon-inducible p204 protein acts as a transcriptional coactivator of Cbfa1 and enhances osteoblast differentiation. J Biol Chem. 2005;280(4):2788–96.

Article  CAS  PubMed  Google Scholar 

Damerau A, Gaber T, Ohrndorf S, Hoff P. JAK/STAT activation: a general mechanism for bone development, homeostasis, and regeneration. Int J Mol Sci. 2020. https://doi.org/10.3390/ijms21239004.

Article  PubMed  PubMed Central  Google Scholar 

Ciobanu DA, Poenariu IS, Crîngus LI, Vreju FA, Turcu-Stiolica A, Tica AA, et al. JAK/STAT pathway in pathology of rheumatoid arthritis (Review). Exp Ther Med. 2020;20(4):3498–503.

CAS  PubMed  PubMed Central  Google Scholar 

Nishida N, Komatsu Y, Komeda T, Fukuda Y. Interferon-alpha improves bone resorption and osteopenia in patients with chronic hepatitis C. Hepatol Res. 2006;34(4):222–7.

Article  CAS  PubMed  Google Scholar 

Varoglu AO, Varoglu E, Bayraktar R, Aygul R, Ulvi H, Yildirim K. The effect of interferon beta 1B on bone mineral density in multiple sclerosis patients. J Back Musculoskelet Rehabil. 2010;23(1):25–9.

Article  PubMed  Google Scholar 

Nguyen A, Miller WP, Gupta A, Lund TC, Schiferl D, Lam LSK, et al. Open-label pilot study of interferon gamma-1b in patients with non-infantile osteopetrosis. JBMR Plus. 2022;6(3):e10597.

Article  CAS  PubMed  PubMed Central  Google Scholar 

O’Shea JJ, Plenge R. JAK and STAT signaling molecules in immunoregulation and immune-mediated disease. Immunity. 2012;36(4):542–50.

Article  PubMed  PubMed Central  Google Scholar 

Platanias LC. Mechanisms of type-I- and type-II-interferon-mediated signalling. Nat Rev Immunol. 2005;5(5):375–86.

Article  CAS  PubMed  Google Scholar 

Shemesh M, Lochte S, Piehler J, Schreiber G. IFNAR1 and IFNAR2 play distinct roles in initiating type I interferon-induced JAK-STAT signaling and activating STATs. Sci Signal. 2021;14(710):eabe4627.

Article  CAS  PubMed  Google Scholar 

Deng Z, Ng C, Inoue K, Chen Z, Xia Y, Hu X, et al. Def6 regulates endogenous type-I interferon responses in osteoblasts and suppresses osteogenesis. Elife. 2020. https://doi.org/10.7554/eLife.59659.

Article  PubMed  PubMed Central  Google Scholar 

Ivashkiv LB, Donlin LT. Regulation of type I interferon responses. Nat Rev Immunol. 2014;14(1):36–49.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Schindler C, Levy DE, Decker T. JAK-STAT signaling: from interferons to cytokines. J Biol Chem. 2007;282(28):20059–63.

Article  CAS  PubMed  Google Scholar 

Schreiber G, Piehler J. The molecular basis for functional plasticity in type I interferon signaling. Trends Immunol. 2015;36(3):139–49.

Article  CAS  PubMed 

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