Testosterone Regulates Bone Response to Infl ammation

Author(s)

Steffens, J. P. ^{[1, 2]} ; Herrera, B. S. ^[1] ; Coimbra, L. S. ^[2] ; Stephens, D. N. ^[1] ; Rossa, Jr., C. ^[2] ; Spolidorio, L. C. ^[2] ; Kantarci, A. ^[1] ; Van Dyke, T. E. ^[1]

Affiliation

^[1] Forsyth Inst, Dept Appl Oral Sci, Ctr Periodontol, Cambridge, MA - USA

^[2] Sao Paulo State Univ, Dept Physiol & Pathol, Sch Dent Araraquara, UNESP, BR-14801903 Araraquara, SP - Brazil

• Document type: Journal article
• Source: Hormone and Metabolic Research; v. 46, n. 3, p. 193-200, MAR 2014.
• Web of Science Citations: 15

Abstract

This study evaluated the alveolar bone response to testosterone and the impact of Resolvin D2 (RvD2) on testosterone-induced osteoblast function. For the in vivo characterization, 60 male adult rats were used. Treatments established sub-physiologic (L), normal (N), or supra-physiologic (H) concentrations of testosterone. Forty rats were subjected to orchiectomy; 20 rats received periodical testosterone injections while 20 rats received testicular sham-operation. Four weeks after the surgeries, 10 rats in each group received a subgingival ligature around the lower first molars to induce experimental periodontal inflammation and bone loss. In parallel, osteoblasts were differentiated from neonatal mice calvariae and treated with various doses of testosterone for 48h. Cell lysates and conditioned media were used for the determination of alkaline phosphatase, osteocalcin, RANKL, and osteoprotegerin. Micro-computed tomography linear analysis demonstrated that bone loss was significantly increased for both L and H groups compared to animals with normal levels of testosterone. Gingival IL-1 expression was increased in the L group (p<0.05). Ten nM testosterone significantly decreased osteocalcin, RANKL, and OPG levels in osteoblasts; 100nM significantly increased the RANKL:OPG ratio. RvD2 partially reversed the impact of 10nM testosterone on osteocalcin, RANKL, and OPG. These findings suggest that both L and H testosterone levels increase inflammatory bone loss in male rats. While low testosterone predominantly increases the inflammatory response, high testosterone promotes a higher osteoblast-derived RANKL:OPG ratio. The proresolving mediator RvD2 ameliorates testosterone-derived downregulation of osteocalcin, RANKL, and OPG in primary murine osteoblasts suggesting a direct role of inflammation in osteoblast function. (AU)

• FAPESP's process: 10/12021-4 - Effect of the testosterone levels reduction on the immunoinflammatory response associated with periodontal disease and rheumatoid arthritis induction in orchiectomized adult male rats
• Grantee: Luis Carlos Spolidorio
• Support Opportunities: Regular Research Grants
• FAPESP's process: 10/09658-0 - Effect of the reduction of testosterone level in the imunoinflammatory responses associated to periodontal disease and reumathoid arthritis due orquiectomy in rats
• Grantee: João Paulo Steffens
• Support Opportunities: Scholarships in Brazil - Doctorate