Expression of sclerostin in the regenerating scales of goldfish and its increase under microgravity during space flight

Abstract

Osteocytes, osteoblasts (bone-forming cells), and osteoclasts (bone-resorbing cells) are the primary types of cells that regulate bone metabolism in mammals. Sclerostin produced in bone cells activates osteoclasts, inhibiting bone formation; excess production of sclerostin, therefore, leads to the loss of bone mass. Fish scales have been reported to have morphological and functional similarities to mammalian bones, making them a useful experimental system for analyzing vertebrate bone metabolism in vitro. However, whether fish scales contain cells producing sclerostin and/or osteocytes has not been determined. The current study demonstrated, for the first time, that sclerostin-containing cells exist in goldfish scales. Analysis of the distribution and shape of sclerostin-expressing cells provided evidence that osteoblasts produce sclerostin in goldfish scales. Furthermore, our results found that osteocyte-like cells exist in goldfish scales, which also produce sclerostin. Finally, we demonstrated that microgravity in outer space increased the level of sclerostin in the scales of goldfish, a finding suggesting that the induction of sclerostin is the mechanism underlying the activation of osteoclasts under microgravity.

Activation of RANKL-producing cells under simulated microgravity with a three-dimensional clinostat in regenerating goldfish scales

“…Teleost scales are a simple calcified tissue in which osteoblasts, osteoclasts, and bone matrix coexist. Furthermore, we recently found that there are two types of osteocyte-like cells in the osseous layer through observation under a transmission electron microscope (Yamamoto et al, 2020a). Moreover, one type was observed at the bottom of the groove, in contact with the collagen bundles of the fibrous layer, whereas the mineralized matrix almost surrounded the other type.…”

“…Therefore, in our co-culture system, osteoblasts and osteoclasts present in the scales sensitively responded to a very low degree of acceleration and simulated microgravity. We strongly believe that the osteocyte-like cells in the osseous layers (Yamamoto et al, 2020a) respond to physical stimuli as mammalian osteocytes do (Nakashima et al, 2011).…”

“…A previous study successfully demonstrated the production of an antiserum against goldfish RANKL in rabbits and detected RANKL-producing cells in regenerating goldfish scales with osteoclasts, osteoblasts, and osteocyte-like cells (Yamamoto et al, 2020a;Yamamoto et al, 2020b). Therefore, the activation of RANKL-producing cells under microgravity can be observed using the regenerating goldfish scales.…”

Glyoxal‐induced formation of advanced glycation end‐products in type 1 collagen decreases both its strength and flexibility in vitro

“…Our recent study using goldfish scales in outer space uncovered the molecular mechanism underlying microgravity-induced osteoporosis-like loss of bone mass in astronauts [24][25][26] . Furthermore, the current study established in vitro systems for analyzing the formation of AGEs in type 1 collagen and the effects of carbonyl compounds on the characteristics of collagen, thereby significantly increasing the value of fish scales for analyzing bone diseases and their association with other pathologies, such as hyperglycemic disease.…”

Osteocytes and Weightlessness

“…Surprisingly, to the best of our knowledge, no data on SOST expression in the long bones of mice subjected to space flight are available in literature. Regenerating goldfish scales incubated during 86 h in the ISS under microgravity conditions demonstrated increased SOST expression in both osteoblast and osteocyte-like cells [ 22 ]. Sclerostin-positive osteocytes were found increased in the cortex of the proximal tibial metaphysis of 2-week HU mice [ 23 ].…”