The Effect of Supra‐ and Subphysiologic Testosterone Levels on Ligature‐Induced Bone Loss in Rats — A Radiographic and Histologic Pilot Study

Steffens, João Paulo; Coimbra, Leila S.; Lucas, Pablo Dallari Ramalho; Rossa, Carlos; Spolidório, Luís Carlos

doi:10.1902/jop.2012.110658

Cited by 18 publications

(34 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This group of people generally use the compounds at concentrations of 10–100 times higher than normal [37]. We have recently shown that serum concentration of testosterone was approximately 7 nM in rats; a 10-fold reduction in these levels can be obtained following orchiectomy as a model of late onset hypogonadism in a rat model [34]. In parallel, the findings from our previous study and the current work showed that rats can be used for low or high levels of testosterone studies, with the advantage of enabling evaluation of the hormonal imbalances in vivo and ex vivo analyses [34].…”

Section: Resultsmentioning

confidence: 99%

“…We have recently shown that serum concentration of testosterone was approximately 7 nM in rats; a 10-fold reduction in these levels can be obtained following orchiectomy as a model of late onset hypogonadism in a rat model [34]. In parallel, the findings from our previous study and the current work showed that rats can be used for low or high levels of testosterone studies, with the advantage of enabling evaluation of the hormonal imbalances in vivo and ex vivo analyses [34]. Our results also reveal that testosterone modulates periodontal bone loss in an inflammatory environment without resulting in any significant change in healthy animals.…”

Section: Resultsmentioning

confidence: 99%

“…After the procedure, the animals were kept in individual cages for 7 days for recovery. As a model for “high testosterone (High)”, we have used a method that was previously described [32–34]. This approach involves orchiectomy followed by an exogenous administration of testosterone.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Testosterone Regulates Bone Response to Inflammation

Steffens

Herrera²,

Coimbra

et al. 2014

Horm Metab Res

View full text Add to dashboard Cite

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 48 h. 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-1β expression was increased in the L group (p < 0.05). Ten nM testosterone significantly decreased osteocalcin, RANKL, and OPG levels in osteoblasts; 100 nM significantly increased the RANKL:OPG ratio. RvD2 partially reversed the impact of 10 nM 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.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Testosterone Regulates Bone Response to Inflammation

Steffens

Herrera²,

Coimbra

et al. 2014

Horm Metab Res

View full text Add to dashboard Cite

show abstract

“…Many in vitro studies assess the role of androgens on different periodontal soft tissue cells: in gingival connective tissue testosterone inhibits prostaglandin formation [26], in inflamed gingiva androgens increase 5-alpha-reductase activity [27]; and in fibroblasts, increasing concentrations of androgens inhibit IL-6 production [28, 29] and increase cell proliferation [30]. Previous studies have demonstrated that low and high testosterone levels in rats increase both gingival and connective tissue areas [13], increase periodontal bone loss; and impact the release of RANKL and osteoprotegerin by murine osteoblasts [14]. …”

Section: Discussionmentioning

confidence: 99%

“…This overproduction leads to tissue breakdown and the consequent resorption of the alveolar process, a bone structure consisting of outer cortical plates of compact bone, a central spongiosa (trabecular bone), and bone lining the alveolus (alveolar bone) [21]. Our previous studies suggest that both low and high testosterone levels regulate experimental bone loss in rats [13, 14]. This study tests the hypothesis that testosterone suppression increases inflammation-induced bone loss through the reduction of androgen receptor activation.…”

Section: Introductionmentioning

confidence: 99%

Androgen receptors and experimental bone loss — an in vivo and in vitro study

Steffens

Coimbra

Rossa

et al. 2015

Bone

Self Cite

View full text Add to dashboard Cite

Testosterone is a sex hormone that exhibits many functions beyond reproduction; one such function is the regulation of bone metabolism. The role played by androgen receptors during testosterone-mediated biological processes associated with bone metabolism is largely unknown. This study aims to use a periodontal disease model in vivo in order to assess the involvement of androgen receptors on microbial-induced inflammation and alveolar bone resorption in experimental bone loss. The impact of hormone deprivation was tested through both orchiectomy and chemical blockage of androgen receptor using flutamide (FLU). Additionally, the direct effect of exogenous testosterone, and the role of the androgen receptor, on osteoclastogenesis were investigated. Thirty male adult rats (n=10/group) were subjected to: 1- orchiectomy (OCX); 2- OCX sham-surgery; or 3- OCX sham-surgery plus FLU, four weeks before the induction of experimental bone loss. Ten OCX sham-operated rats were not subjected to experimental bone loss and served as healthy controls. The rats were euthanized two weeks later, so as to assess bone resorption and the production of inflammatory cytokines in the gingival tissue and serum. In order to study the in vitro impact of testosterone, osteoclasts were differentiated from RAW264.7 cells and testosterone was added at increasing concentrations. Both OCX and FLU increased bone resorption, but OCX alone was observed to increase osteoclast count. IL-1β production was increased only in the gingival tissue of OCX animals, whereas FLU-treated animals presented a decreased expression of IL-6. Testosterone reduced the osteoclast formation in a dose-dependent manner, and significantly impacted the production of TNF-α; FLU partially reversed these actions. When taken together, our results indicate that testosterone modulates experimental bone loss, and that this action is mediated, at least in part, via the androgen receptor.

show abstract