Deletion of IL-17ra in osteoclast precursors increases bone mass by decreasing osteoclast precursor abundance

• Type of Material: Article
• Authors: Joseph L Roberts, Emory University; Giovanni Mella-Velazquez, Emory University; Hamid Dar, Emory University; Guanglu Liu, The Atlanta Department of Veterans Affairs Medical Center, Decatur; Hicham Drissi, Emory University
• Language: English
• Date: 2022-04-01
• Publisher: ELSEVIER SCIENCE INC
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2021 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.bone.2021.110310
• Title of Journal or Parent Work: BONE
• Volume: 157
• Start Page: 116310
• End Page: 116310
• Grant/Funding Information: This work was supported by the National Institutes of Health (R01 AG064464), Veterans Health Administration (I01BX004708), and Emory University.
• Keywords: OSTEOPOROSIS; IL-17a; Endocrinology & Metabolism; STIMULATION; RECEPTOR; Science & Technology; CYTOKINES; Inflammation; Bone resorption; SERUM-LEVELS; AGE; Bone turnover; Cytokine; INTERLEUKIN-17; LIGAND; RESORPTION; Life Sciences & Biomedicine

Abstract

Metabolic bone diseases, such as osteoporosis, typically reflect an increase in the number and activity of bone-resorbing osteoclasts that result in a loss of bone mass. Inflammatory mediators have been identified as drivers of both osteoclast formation and activity. The IL-17 family of inflammatory cytokines has gained attention as important contributors to both bone formation and resorption. The majority of IL-17 cytokines signal through receptor complexes containing IL-17a receptor (IL-17ra); however, the role of IL-17ra signaling in osteoclasts remains elusive. In this study, we conditionally deleted Il17ra in osteoclast precursors using LysM-Cre and evaluated the phenotypes of skeletally mature male and female conditional knockout and control mice. The conditional knockout mice displayed an increase in trabecular bone microarchitecture in both the appendicular and axial skeleton. Assessment of osteoclast formation in vitro revealed that deletion of Il17ra decreased osteoclast number, which was confirmed in vivo using histomorphometry. This phenotype was likely driven by a lower abundance of osteoclast precursors in IL-17ra conditional knockout mice. This study suggests that IL-17ra signaling in preosteoclasts can contribute to osteoclast formation and subsequent bone loss.