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Spaceflight is known to induce severe systemic bone loss and muscle atrophy of astronauts due to the circumstances of microgravity. We examined the influence of artificially produced 2G hypergravity on mice for bone and muscle mass with newly developed centrifuge device. We also analyzed the effects of microgravity (mostly 0G) and artificial produced 1G in ISS (international space station) on mouse bone mass. Experiment on the ground, the bone mass of humerus, femur and tibia was measured using micro-computed tomography (μCT), and the all bone mass was significantly increased in 2G compared with 1G control. In tibial bone, the mRNA expression of bone formation related genes such as Osx and Bmp2 was elevated. The volume of triceps surae muscle was also increased in 2G compared with 1G control, and the mRNA expression of myogenic factors such as Myod and Myh1 was elevated by 2G. On the other hand, microgravity in ISS significantly induced the loss of bone mass on humerus and tibia, compared with artificial 1G induced by centrifugation. Here, we firstly report that bone and muscle mass are regulated by the gravity with loaded force in both of positive and negative on the ground and in the space.

Abstract. Nobiletin, a polymethoxy flavonoid, prevents cancer and inflammation, but the roles of nobiletin in bone are unclear. We examined the effects of nobiletin on bone resorption in vitro and on bone mass in ovariectomized (OVX) mice in vivo. In vitro, nobiletin suppressed osteoclast formation and bone resorption induced by interleukin (IL)-1. Nobiletin suppressed the expression of cyclooxygenase-2, NFκB-dependent transcription, and prostaglandin E (PGE) production induced by IL-1 in osteoblasts. OVX mice showed severe bone loss in the femur by increased bone resorption due to estrogen deficiency, and nobiletin significantly restored the bone mass. Nobiletin could be beneficial to bone health in postmenopausal women.

Abnormalities of bone turnover are commonly observed in patients with chronic kidney disease ( CKD ), and the low‐turnover bone disease is considered to be associated with low serum parathyroid hormone ( PTH ) levels and skeletal resistance to PTH . Indoxyl sulfate (IS) is a representative uremic toxin that accumulates in the blood of patients with CKD . Recently, we have reported that IS exacerbates low bone turnover induced by parathyroidectomy (PTX) in adult rats, and suggested that IS directly induces low bone turnover through the inhibition of bone formation by mechanisms unrelated to skeletal resistance to PTH . To define the direct action of IS in bone turnover, we examined the effects of IS on bone formation and bone resorption in vitro . In cultures of mouse primary osteoblasts, IS suppressed the expression of osterix, osteocalcin, and bone morphogenetic protein 2 (BMP2) mRNA and clearly inhibited the formation of mineralized bone nodules. Therefore, IS directly acts on osteoblastic cells to suppress bone formation. On the other hand, IS suppressed interleukin ( IL )‐1‐induced osteoclast formation in cocultures of bone marrow cells and osteoblasts, and IL ‐1‐induced bone resorption in calvarial organ cultures. In cultures of osteoblasts, IS suppressed the mRNA expression of RANKL , the receptor activator of NF ‐κB ligand, which is a pivotal factor for osteoclast differentiation. Moreover, IS acted on osteoclast precursor, bone marrow‐derived macrophages and RAW 264.7 cells, and suppressed RANKL ‐dependent differentiation into mature osteoclasts. IS may induce low‐turnover bone disease in patients with CKD by its direct action on both osteoblasts and osteoclast precursors to suppress bone formation and bone resorption.

HighlightsWe examine the role of EGCG, a major polyphenol in green tea, in bone metabolism.LPS is a pathogen-associated molecule, and induces inflammatory bone resorption.EGCG suppresses the LPS-induced PGE production in osteoblasts.EGCG suppresses the LPS-induced bone resorption of alveolar bones in vitro.In the mouse model of periodontitis, EGCG restores the loss of alveolar bone mass.