Date of this Version
Journal of Bone and Mineral Research
Long-term administration of nitrogen-containing bisphosphonates can induce detrimental side effects such as bisphosphonate-related osteonecrosis of the jaw (BRONJ) in human. Although inflammation is known to be associated with BRONJ development, the detailed underlying mechanism remains unknown. Here, we report that the pro-inflammatory cytokine IL-36α is, in part, responsible for the BRONJ development. We found a notably higher level of IL-36α and lower level of collagen in the BRONJ lesions in mice. We also found that IL-36α remarkably suppressed TGF-β-mediated expression of Collα1 and α-Sma via the activation of Erk signaling pathway in mouse gingival mesenchymal stem cells. When IL-36 signaling was abrogated in vivo, development of BRONJ lesions was ameliorated in mice. Taken together, we showed the pathologic role of IL-36α in BRONJ development by inhibiting collagen expression and demonstrated that IL-36α could be a potential marker and a therapeutic target for the prevention and treatment of BRONJ.
This is the pre-peer reviewed version of the following article: [Kim, S., Williams, D. W., Lee, C., Kim, T., Arai, A., Shi, S., . . . Kim, R. H. (2017). IL-36 induces bisphosphonate-related osteonecrosis of the jaw-like lesions in mice by inhibiting TGF-β-mediated collagen expression: IL-36 MEDIATES BRONJ LESIONS IN MICE. Journal of Bone and Mineral Research, 32(2), 309-318. doi:10.1002/jbmr.2985], which has been published in final form at [http://dx.doi.org/10.1002/jbmr.2985]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
IL-36, OSTEONECROSIS OF THE JAW, BISPHOSPHONATE, COLLAGEN, TGF-β, Erk
Kim, S., Williams, D. W., Williams, C., Kim, T., Arai, A., Shi, S., Li, X., Shin, K., Kang, M. K., Park, N., & Kim, R. H. (2017). IL-36 Induces Bisphosphonate-Related Osteonecrosis of the Jaw-Like Lesions in Mice by Inhibiting TGF-β-Mediated Collagen Expression. Journal of Bone and Mineral Research, 32 (2), 309-318. http://dx.doi.org/10.1002/jbmr.2985
Date Posted: 01 March 2022
This document has been peer reviewed.