Thyroid hormones are critical regulators of bone metabolism. Their cellular import is guided through transporter proteins, including the monocarboxylate transporter 8 (MCT8). Conditional Mct8 knockout in osteoblast and osteoclast precursors leads to trabecular bone gain in 12-week-old male mice. Given that thyroid hormones regulate both skeletal development and bone maintenance, we investigated the effect of bone cell-specific Mct8 deletion in 6-week-old (young) and 24-week-old (adult) male mice.

Mct8 ablation in osteoclast precursors led to trabecular bone gain at the spine in 6-week-old animals compared to age-matched controls, whereas adult animals displayed a shift towards trabecular bone loss in both femur and vertebra. Mct8 deficiency in osteoprogenitors increased osteoblast numbers and trabecular bone mass at the spine of young mice, without skeletal differences between adult knockout mice and littermate controls. In contrast, young mice lacking Mct8 in late osteoblasts/osteocytes exhibited lower trabecular bone volume at the spine and femur compared to respective controls, but no differences were detected at 24 weeks of age. In vitro studies of osteoblasts with Dmp1-Cre promotor driven Mct8 deletion showed no significant alterations of osteogenic marker gene expression and mineralization capacity suggesting that MCT8 is not crucial for osteoblast maturation.

Overall, we observed mild effects with conditional Mct8 knockout on bone microarchitecture and bone turnover especially during growth implying a secondary role for MCT8 as a thyroid hormone transporter in bone.