title: Thyroid hormone receptor β mediates thyroid hormone effects on bone remodeling and bone mass.
abstract: Excess thyroid hormone (TH) in adults causes osteoporosis and increases fracture risk. However, the mechanisms by which TH affects bone turnover are not elucidated. In particular, the roles of thyroid hormone receptor (TR) isotypes in the mediation of TH effects on osteoblast-mediated bone formation and osteoclast-mediated bone resorption are not established. In this study we have induced experimental hypothyroidism or hyperthyroidism in adult wild-type, TRα- or TRβ-deficient mice and analyzed the effects of TH status on the structure and remodeling parameters of trabecular bone. In wild-type mice, excess TH decreased bone volume and mineralization. High TH concentrations were associated with a high bone-resorption activity, assessed by increased osteoclast surfaces and elevated concentrations of serum bone-resorption markers. Serum markers of bone formation also were higher in TH-treated mice. TRα deficiency did not prevent TH action on bone volume, bone mineralization, bone formation, or bone resorption. In contrast, TRβ deficiency blocked all the early effects of excess TH observed in wild-type mice. However, prolonged exposure to low or high TH concentrations of TRβ-deficient mice induced mild modifications of bone structure and remodeling parameters. Together our data suggest that TRβ receptors mediate the acute effects produced by transient changes of TH concentrations on bone remodeling, whereas TRα receptors mediate long-term effects of chronic alterations of TH metabolism. These data shed new light on the respective roles of TRs in the control of bone metabolism by TH.
authors: INSERM, U577, and University Victor Segalen, Bordeaux, France.
authors: Laurent-Emmanuel
authors: LE
authors: Monfoulet
authors: Bénédicte
authors: B
authors: Rabier
authors: Romain
authors: R
authors: Dacquin
authors: Adrienne
authors: A
authors: Anginot
authors: Johan
authors: J
authors: Photsavang
authors: Pierre
authors: P
authors: Jurdic
authors: Laurence
authors: L
authors: Vico
authors: Luc
authors: L
authors: Malaval
authors: Olivier
authors: O
authors: Chassande