Stanniocalcin in the Corpuscles of Stannius Inhibits the Osteoclastic Activation by Regulating the Rankl/Opg Expression

Background: The corpuscles of Stannius (CS) are endocrine glands that regulate homeostasis of minerals, including calcium and phosphate, in bony fish. The hormone secreted by the CS, known as stanniocalcin, has been found in humans and bony fish. In mammals, stanniocalcin expressed in osteoblasts and has been reported to regulate osteoblastic differentiation. However, the details regarding its effect on osteoclasts remain uninvestigated. Therefore, in this study, we aimed to evaluate the effects of stanniocalcin on bone metabolism, including osteoclasts.Methods: Stanniocalcin is composed of approximately 250 amino acids, including several cysteines and glycans. Artificially synthesizing this hormone is difficult. In the present study, we used the CS extract to evaluate the effects of stanniocalcin on bone metabolism. Moreover, we established an in vitro bioassay system utilizing goldfish scales as a coexistence model of osteoblasts (bone-forming cells) and osteoclasts (bone-resorbing cells) in the calcified bone matrix. Using the goldfish scales, we examined the effects of CS extract treatment on the mRNA expressions of osteoclast-and osteoblast-related genes. Furthermore, to assess the inhibitory action of osteoclasts, we examined the receptor activator for NF-kappa B ligand (Rankl), osteoclastogenesis-promoting factor, osteoprotegerin (Opg), osteoclastogenesis inhibition factor, involved in the osteoblast-osteoclast interaction.Results: The expression of osteoblastic markers, such as alkaline phosphatase and collagen type I alpha 1 (Col1a1), significantly increased 6 h post-treatment with the CS extract. At 18 h post-incubation, Col1a1 and osteocalcin mRNA expressions in the treated scales also significantly upregulated. Conversely, at 6 and 18 h post-incubation, the mRNA expression of osteoclastic markers, cathepsin K, tartrate-resistant acid phosphatase, and matrix metalloproteinase-9, significantly decreased. Further, at 6 h post-incubation, Rankl/Opg expression significantly decreased on adding the CS extract. Conclusions: The CS extract was found to inhibit the osteoclastic activity by modulating Rankl/Opg expression. Thus, stannio-calcin inhibits the osteoclastic activity but promotes osteoblastic activity and bone formation.