Search

This study investigated the effects of blockade of IL-6 on bone loss induced by modeled microgravity (MG). Adult male mice were exposed to hind-limb suspension (HLS) and treated with IL-6-neutralizing antibody (IL-6 nAb) for 4 weeks. HLS in mice led to upregulation of IL-6 expression in both sera and femurs. IL-6 nAb treatment in HLS mice significantly alleviated bone loss, evidenced by increased bone mineral density of whole tibia, trabecular thickness and number, bone volume fraction of proximal tibiae, and ultimate load and stiffness of femoral diaphysis. IL-6 nAb treatment in HLS mice significantly enhanced levels of osteocalcin in sera and reduced levels of deoxypyridinoline. In MC3T3-E1 cells exposed to MG in vitro, IL-6 nAb treatment increased mRNA expression and activity of alkaline phosphatase, mRNA expression of osteopontin and runt-related transcription factor 2, and protein levels of osteoprotegerin and decreased protein levels of receptor activator of the NF-[kappa]B ligand. In RAW254.7 cells exposed to MG, IL-6 nAb treatment downregulated mRNA expression of cathepsin K and tartrate-resistant acid phosphatase (TRAP) and reduced numbers ofTRAP-positive multinucleated osteoclasts. In conclusion, blockade of IL-6 alleviated the bone loss induced by MG. Key words: microgravity, bone loss, IL-6, osteoblastogenesis, osteoclastogenesis. Cette etude portait sur les effets de l'inhibition de l'IL-6 sur la perte osseuse dans un modele de microgravite (MG). Nous avons mis la patte posterieure de souris adultes males en suspension (SPP) et administre un anticorps neutralisant l'IL-6 (IL-6 nAb) pendant 4 semaines. La SPP chez les souris a mene a une regulation a la hausse de l'expression de l'IL-6 dans le serum comme dans le femur. L'administration d'IL-6 nAb chez les souris SPP a permis d'attenuer la perte osseuse de facon marquee, phenomene mis en evidence par une augmentation de la densite minerale osseuse du tibia entier, de l'epaisseur des trabecules et de leur nombre, de la fraction de volume osseux dans le tibia proximal, ainsi que de la charge ultime et de la rigidite de la diaphyse femorale. L'administration d'IL-6 nAb chez les souris SPP a entraine une hausse notable des taux d'osteocalcine dans le serum, avec une diminution des taux de desoxypyridinoline. Dans les cellules MC3T3-E1 exposees a la MG in vitro, l'administration d'IL-6 nAb entrainait une augmentation de l'expression en ARNm et de l'activite de la phosphatase alcaline, de l'expression en ARNm de l'osteopontine et du facteur de transcription lie a Runt 2, et des taux en proteines d'osteoproteregine, avec une diminution des taux en proteines de l'activateur du recepteur du ligand du NF-[kappa]B. Dans les cellules RAW254.7 exposees a la MG, l'administration d'IL-6 nAb entrainait une regulation a la baisse de l'expression en ARNm de la cathepsine K et de la phosphatase acide resistante au tartrate (ou TRAP pour << tartrate-resistant acid phosphatase >>) avec une diminution du nombre d'osteoclastes multinuclees reagissant a la TRAP. En conclusion, l'inhibition de l'IL-6 permettait d'attenuer la perte osseuse engendree par la MG. [Traduit par la Redaction] Mots-cles: microgravite, perte osseuse, IL-6, osteoblastogenese, osteoclastogenese., Introduction Bone loss caused by microgravity in astronauts poses a significant risk to the health and is known as a significant barrier for long-duration spaceflight (Grimm et al. 2016). The [...]

The present study was undertaken to explore the therapeutic potential of hydrogen sulfide against bone loss induced by modeled microgravity. Hindlimb suspension (HLS) and rotary wall vessel bioreactor were applied to model microgravity in vivo and in vitro, respectively. Treatment of rats with GYY4137 (a water soluble donor of hydrogen sulfide, 25 mg/kg per day, i.p.) attenuated HLS-induced reduction of bone mineral density in tibiae, and preserved bone structure in tibiae and mechanical strength in femurs. In HLS group, GYY4137 treatment significantly increased levels of osteocalcin in sera. Interestingly, treatment of HLS rats with GYY4137 enhanced osteoblast surface, but had no significant effect on osteoclast surface of proximal tibiae. In MC3T3-E1 cells exposed to modeled microgravity, GYY4137 stimulated transcriptional levels of runt-related transcription factor 2 and enhanced osteoblastic differentiation, as evidenced by increased mRNA expression and activity of alkaline phosphatase. HLS in rats led to enhanced levels of interleukin 6 in sera, skeletal muscle, and tibiae, which could be attenuated by GYY4137 treatment. Our study showed that GYY4137 preserved bone structure in rats exposed to HLS and promoted osteoblastic differentiation in MC3T3-E1 cells under modeled microgravity. Key words: microgravity, rotary wall vessel bioreactor, hydrogen sulfide, interleukin 6, osteoblast. La presente etude a ete entreprise en vue d'explorer le potentiel therapeutique du sulfure d'hydrogene contre la perte osseuse obtenue dans un modele de microgravite. Nous avons applique une suspension du membre posterieur (SMP) et un bioreacteur rotatif sur paroi vasculaire dans des modeles de microgravite in vivo et in vitro, respectivement. L'administration a des rats de GYY4137 (un donneur de sulfure d'hydrogene hydrosoluble, 25 mg/kg par jour, i.p.) permettait d'attenuer la diminution de la densite osseuse du tibia provoquee par la SMP et de preserver la structure osseuse du tibia, ainsi que la resistance mecanique des femurs. Dans le groupe SMP, l'administration de GYY4137 entrainait une augmentation notable des taux d'osteocalcine dans le serum. Il est interessant de noter que l'administration de GYY4137 chez les rats SMP entrainait une augmentation de la surface des osteoblastes, mais sans effet notable sur la surface des osteoclastes dans le tibia proximal. Dans les cellules MC3T3-E1 exposees a la microgravite experimentale, le GYY4137 entrainait une stimulation des taux de transcription du Runx2 (pour << runt-related transcription factor 2 >>), avec une augmentation de la differentiation en osteoblastes, mises en evidence par une augmentation de l'expression en ARNm et de l'activite de la phosphatase alcaline. Chez les rats, la SMP a mene a une hausse des taux d'interleukine 6 dans le serum, le muscle squelettique et les tibias, laquelle pouvait etre attenuee par l'administration de GYY4137. Notre etude a montre que le GYY4137 permettait de preserver la structure osseuse chez des rats exposes a la SMP, ainsi que de favoriser la differentiation en osteoblaste de cellules MC3T3-E1 soumises a la microgravite experimentale. [Traduit par la Redaction] Mots-cles : microgravite, bioreacteur rotatif sur paroi vasculaire, sulfure d'hydrogene, interleukine 6, osteoblaste., Introduction Disuse-induced bone loss not only threatens the health of astronauts during space flight, but also increases the susceptibility to fractures in individuals requiring prolonged bed rest (Zhang et al. [...]

The characteristics of dissemination and universal application of social media bring new opportunities for multiple arenas (such as government, social institutions, and the public) to participate in the governance of public crises. During China’s prevention and control of COVID-19, social media functioned well in the governance of the pandemic. This paper mainly analyzes the role of social media in crisis management from the perspectives of risk communication, social reconstruction, collaborative governance, etc., thereby providing the government with recommendations for the improved employment of social media and improving the public crisis response.

Mono-ADP-ribosylation (MARylation) is a post-translational modification that regulates a variety of biological processes, including DNA damage repair, cell proliferation, metabolism, and stress and immune responses. In mammals, MARylation is mainly catalyzed by ADP-ribosyltransferases (ARTs), which consist of two groups: ART cholera toxin-like (ARTCs) and ART diphtheria toxin-like (ARTDs, also known as PARPs). The human ARTC (hARTC) family is composed of four members: two active mono-ADP-ARTs (hARTC1 and hARTC5) and two enzymatically inactive enzymes (hARTC3 and hARTC4). In this study, we systematically examined the homology, expression, and localization pattern of the hARTC family, with a particular focus on hARTC1. Our results showed that hARTC3 interacted with hARTC1 and promoted the enzymatic activity of hARTC1 by stabilizing hARTC1. We also identified vesicle-associated membrane protein-associated protein B (VAPB) as a new target of hARTC1 and pinpointed Arg50 of VAPB as the ADP-ribosylation site. Furthermore, we demonstrated that knockdown of hARTC1 impaired intracellular calcium homeostasis, highlighting the functional importance of hARTC1-mediated VAPB Arg50 ADP-ribosylation in regulating calcium homeostasis. In summary, our study identified a new target of hARTC1 in the endoplasmic reticulum and suggested that ARTC1 plays a role in regulating calcium signaling. [ABSTRACT FROM AUTHOR]