Thyroid hormone receptor β mediates thyroid hormone effects on bone remodeling and bone mass

Area of Science:

• Endocrinology
• Bone Biology
• Molecular Endocrinology

Background:

• Excess thyroid hormone (TH) is linked to osteoporosis and increased fracture risk in adults.
• The precise mechanisms by which TH influences bone turnover, particularly the roles of specific thyroid hormone receptor (TR) isotypes, remain unclear.
• Understanding TR isotype roles is crucial for elucidating TH effects on osteoblast-mediated bone formation and osteoclast-mediated bone resorption.

Purpose of the Study:

• To investigate the distinct roles of TRα and TRβ in mediating the effects of TH on bone structure and remodeling.
• To analyze how altered TH status (hypothyroidism and hyperthyroidism) impacts bone turnover parameters in mice lacking TRα or TRβ.
• To differentiate the short-term and long-term effects of TH on bone metabolism mediated by different TRs.

Main Methods:

• Induction of experimental hypothyroidism and hyperthyroidism in adult wild-type, TRα-deficient, and TRβ-deficient mice.
• Analysis of trabecular bone structure and remodeling parameters, including bone volume and mineralization.
• Assessment of bone resorption and formation markers in serum and via osteoclast surface analysis.

Main Results:

• In wild-type mice, excess TH reduced bone volume and mineralization, increasing bone resorption and formation markers.
• TRα deficiency did not prevent TH-induced changes in bone volume, mineralization, formation, or resorption.
• TRβ deficiency abolished the acute effects of excess TH on bone remodeling, though prolonged TH alterations caused mild bone modifications in TRβ-deficient mice.

Conclusions:

• Thyroid hormone receptor beta (TRβ) is the primary mediator of acute effects of TH on bone remodeling.
• Thyroid hormone receptor alpha (TRα) appears to mediate long-term effects of chronic TH alterations on bone metabolism.
• These findings elucidate the differential roles of TR isotypes in TH-regulated bone metabolism, offering insights into osteoporosis associated with TH imbalances.