Thyroid and bone: macrophage-derived TSH-β splice variant increases murine osteoblastogenesis

Area of Science:

• Endocrinology
• Bone Biology
• Cell Biology

Background:

• Thyroid-stimulating hormone (TSH) influences bone physiology by affecting osteoblasts and osteoclasts.
• The direct in vivo role of pituitary-derived TSH in bone protection remains uncertain.
• A novel TSH-β subunit variant (TSH-βv) is produced by bone marrow cells.

Purpose of the Study:

• To characterize the functional relevance of the TSH-βv produced by bone marrow cells.
• To investigate the bioactivity and local effects of TSH-βv on bone cells.
• To explore a potential local TSH signaling pathway in bone metabolism.

Main Methods:

• Bone marrow-derived macrophages (MØs) were isolated and characterized for TSH-βv production.
• MØs were cocultured with Chinese Hamster Ovary (CHO) cells expressing the TSH receptor to assess TSH-βv bioactivity (cAMP production).
• MØs and osteoblasts were cocultured to evaluate effects on osteoblastogenesis, with experiments using anti-TSH-β antibody and electron microscopy.

Main Results:

• Bone marrow-derived macrophages preferentially produced TSH-βv.
• TSH-βv exhibited bioactivity, stimulating intracellular cAMP production in TSH receptor-expressing cells.
• Coculture of MØs and osteoblasts enhanced osteoblastogenesis, an effect reduced by anti-TSH-β antibody.
• Direct interaction between MØs and osteoblasts was observed via electron microscopy.

Conclusions:

• A novel TSH-like molecule (TSH-βv) derived from macrophages locally modulates bone biology.
• This macrophage-derived TSH-βv promotes osteoblastogenesis, suggesting a local mechanism for bone protection.
• The findings raise questions about the relative contributions of local versus pituitary-derived TSH in maintaining bone health.