Kanazawa University-led team reveals melanin-concentrating hormone regulates bone cell activity and calcium metabolism in goldfish scales

A collaborative research group led by Professor Nobuo Suzuki of Kanazawa University’s Institute of Nature and Environmental Technology, together with Kohei Kuroda, Satsuki Kimura, and researchers from Kitasato University, Bunkyo University, and Rikkyo University, has clarified for the first time how melanin-concentrating hormone acts on fish bone by using goldfish scales as a bone model. When goldfish scales were cultured with melanin-concentrating hormone, short-term treatment suppressed osteoclast-related gene expression and inhibited bone resorption. In contrast, administration every other day for 10 days activated osteoclasts and caused calcium release in regenerating scales, while also increasing blood calcium levels and promoting calcitonin secretion. These findings indicate that melanin-concentrating hormone may suppress bone resorption in the short term but indirectly promote it under longer-term treatment conditions. Fish scales contain osteoblasts, osteoclasts, and osteocytes, and undergo bone metabolism similarly to human bone. The study suggests that melanin-concentrating hormone acts on these cells to regulate both bone formation and bone resorption. Melanin-concentrating hormone has long been known in fish as a hormone that controls body color changes by aggregating pigment granules in the epidermis. More recently, it has also been linked to sleep, feeding, and energy metabolism. Another pigment-regulating hormone, melanocyte-stimulating hormone, acts antagonistically by promoting pigment dispersion and has been reported to affect bone metabolism in fish and mammals. In mammals, melanin-concentrating hormone is thought to help maintain bone mass by suppressing osteoclast activity, but the detailed mechanisms by which it acts on bone-forming and bone-resorbing cells have remained unclear. In this study, the researchers used goldfish scales as a model for bone metabolism and examined how melanin-concentrating hormone affects osteoblasts, osteoclasts, and calcium regulation. In cultured goldfish scales, the hormone suppressed osteoclast-related genes such as atp6v0d2 and reduced the rankl/opg ratio, an osteoblast-mediated signal for osteoclast formation, indicating an inhibitory effect on osteoclast function. In live goldfish, 24 hours after administration, plasma calcium concentration and TRAP activity, a marker of osteoclast activity, decreased. This supports the possibility that the hormone acts on osteoclasts in scales and reduces calcium ion release from scales into the bloodstream. Expression analysis of the two goldfish melanin-concentrating hormone receptors, MCHR1 and MCHR2, showed that only MCHR2 was expressed in goldfish scales and in the ultimobranchial gland, the calcitonin-secreting organ, suggesting that the hormone’s effects are mainly mediated through MCHR2. However, when the hormone was repeatedly administered for 10 days to regenerating scales, both ALP activity, a marker of bone formation, and TRAP activity, a marker of bone resorption, increased, showing enhanced bone turnover. At the same time, calcium content in regenerating scales decreased, suggesting suppressed mineralization, while blood calcium and calcitonin concentrations increased, indicating an effect on systemic calcium regulation. Overall, the study shows that melanin-concentrating hormone is a multifaceted regulator of bone cell function and calcium homeostasis in goldfish: it suppresses osteoclast activity under some conditions, while promoting bone turnover depending on administration method and exposure time. Future work will examine whether melanin-concentrating hormone activates osteoclasts under culture conditions longer than six hours and will analyze the time course of osteoclast activation in goldfish scales after administration, with the aim of clarifying the molecular mechanisms that regulate bone formation and bone resorption. The findings were published online in Scientific Reports on March 20, 2026, under the title “Melanin concentrating hormone regulates bone cell activities and calcium metabolism in regenerating goldfish scales,” DOI: 10.1038/s41598-026-41253-4.