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Mechanical forces are essential to maintain skeletal homeostasis, and microgravity exposure leads to bone loss. During space flight, bone mineral density is decreased because of the inactivation of osteoblast and activation of osteoclast. However, the underlying molecular mechanism is still not clear. CD44 acts as a cellular surface adhesion molecule, which plays an important role in signal transduction between cells. Numerous studies have shown that CD44 plays diverse roles in promoting pre-osteoclast fusion. However, the role of CD44 in the alteration of osteoclast function induced by simulated microgravity remains to be fully elucidated. In this work, we utilized a ground-based, microgravity-simulation system, the Rotating Wall Vessel Bioreactor (RWVB). Using the RWVB, we demonstrated that simulated microgravity enhanced osteoclast function, meantime CD44 mRNA and protein levels were significantly increased. To verify the effects of CD44 on alteration of osteoclast function induced by simulated microgravity, specific siRNAs targeting CD44 were transfected. The results showed knockdown of CD44 inhibited the alteration of osteoclast function induced by simulated microgravity. Moreover, we found that clinorotation activated the NF-κB/NFATc1-mediated signaling pathway, which was downregulated after knockdown of CD44. Our study provided evidence that CD44 positively regulated osteoclast function and therapeutic suppression of CD44 may counteract bone loss induced by simulated microgravity. • CD44 was significantly increased in osteoclasts under SMG. • Knockdown of CD44 inhibited the upregulation of osteoclast function under SMG. • CD44 mediated the activation of osteocalsts through NFκB/NFATc1 pathway under SMG. [ABSTRACT FROM AUTHOR]

Objectives: Cardiac Ca2+ signalling plays an essential role in regulating excitation‐contraction coupling and cardiac remodelling. However, the response of cardiomyocytes to simulated microgravity and hypergravity and the effects on Ca2+ signalling remain unknown. Here, we elucidate the mechanisms underlying the proliferation and remodelling of HL‐1 cardiomyocytes subjected to rotation‐simulated microgravity and 4G hypergravity. Materials and Methods: The cardiomyocyte cell line HL‐1 was used in this study. A clinostat and centrifuge were used to study the effects of microgravity and hypergravity, respectively, on cells. Calcium signalling was detected with laser scanning confocal microscopy. Protein and mRNA levels were detected by Western blotting and real‐time PCR, respectively. Wheat germ agglutinin (WGA) staining was used to analyse cell size. Results: Our data showed that spontaneous calcium oscillations and cytosolic calcium concentration are both increased in HL‐1 cells after simulated microgravity and 4G hypergravity. Increased cytosolic calcium leads to activation of calmodulin‐dependent protein kinase II/histone deacetylase 4 (CaMKII/HDAC4) signalling and upregulation of the foetal genes ANP and BNP, indicating cardiac remodelling. WGA staining indicated that cell size was decreased following rotation‐simulated microgravity and increased following 4G hypergravity. Moreover, HL‐1 cell proliferation was increased significantly under hypergravity but not rotation‐simulated microgravity. Conclusions: Our study demonstrates for the first time that Ca2+/CaMKII/HDAC4 signalling plays a pivotal role in myocardial remodelling under rotation‐simulated microgravity and hypergravity. [ABSTRACT FROM AUTHOR]