How are cell and tissue structure and function influenced by gravity and what are the gravity perception mechanisms?

Progress in mechanobiology allowed us to better understand the important role of mechanical forces in the regulation of biological processes. Space research in the field of life sciences clearly showed that gravity plays a crucial role in biological processes. The space environment offers the unique opportunity to carry out experiments without gravity, helping us not only to understand the effects of gravitational alterations on biological systems but also the mechanisms underlying mechanoperception and cell/tissue response to mechanical and gravitational stresses. Despite the progress made so far, for future space exploration programs it is necessary to increase our knowledge on the mechanotransduction processes as well as on the molecular mechanisms underlying microgravity-induced cell and tissue alterations. This white paper reports the suggestions and recommendations of the SciSpacE Science Community for the elaboration of the section of the European Space Agency roadmap “Biology in Space and Analogue Environments” focusing on “How are cells and tissues influenced by gravity and what are the gravity perception mechanisms?” The knowledge gaps that prevent the Science Community from fully answering this question and the activities proposed to fill them are discussed

Musculoskeletal Effects of Altered GH Action

Growth hormone (GH) is a peptide hormone that can signal directly through its receptor or indirectly through insulin-like growth factor 1 (IGF-1) stimulation. GH draws its name from its anabolic effects on muscle and bone but also has distinct metabolic effects in multiple tissues. In addition to its metabolic and musculoskeletal effects, GH is closely associated with aging, with levels declining as individuals age but GH action negatively correlating with lifespan. GH’s effects have been studied in human conditions of GH alteration, such as acromegaly and Laron syndrome, and GH therapies have been suggested to combat aging-related musculoskeletal diseases, in part, because of the decline in GH levels with advanced age. While clinical data are inconclusive, animal models have been indispensable in understanding the underlying molecular mechanisms of GH action. This review will provide a brief overview of the musculoskeletal effects of GH, focusing on clinical and animal models

A bi-lineage conducive scaffold for osteochondral defect regeneration

Because cartilage and bone tissues have different lineage-specific biological properties, it is challenging to fabricate a single type of scaffold that can biologically fulfill the requirements for regeneration of these two lineages simultaneously within osteochondral defects. To overcome this challenge, a lithium-containing mesoporous bioglass (Li-MBG) scaffold is developed. The efficacy and mechanism of Li-MBG for regeneration of osteochondral defects are systematically investigated. Histological and micro-CT results show that Li-MBG scaffolds significantly enhance the regeneration of subchondral bone and hyaline cartilage-like tissues as compared to pure MBG scaffolds, upon implantation in rabbit osteochondral defects for 8 and 16 weeks. Further investigation demonstrates that the released Li+ ions from the Li-MBG scaffolds may play a key role in stimulating the regeneration of osteochondral defects. The corresponding mechanistic pathways involve Li+ ions enhancing the proliferation and osteogenic differentiation of bone mesenchymal stem cells (BMSCs) through activation of the Wnt signalling pathway, as well as Li+ ions protecting chondrocytes and cartilage tissues from the inflammatory osteoarthritis (OA) environment through activation of autophagy. These findings suggest that the incorporation of Li+ ions into bioactive MBG scaffolds is a viable strategy for fabricating bi-lineage conducive scaffolds that enhance regeneration of osteochondral defects

Inhibition of Rac1 activity by controlled release of NSC23766 from chitosan microspheres effectively ameliorates osteoarthritis development in vivo

Background Osteoarthritis (OA) is a degenerative joint disease characterised by cartilage degradation and chondrocyte hypertrophy. A recent study showed that Rac1 promoted expression of MMP13 and chondrocyte hypertrophy within the growth plate. These findings warrant further investigations on the roles of Rac1 in OA development and therapy in animal models. Objective To investigate the role and mechanistic pathway of Rac1 involvement in pathological changes of OA chondrocytes in vitro and OA development in vivo, as well as to develop a strategy of modulating Rac1 activity for OA treatment. Material and methods OA and normal cartilage from human or mice were used for immunohistochemical study and Rac1 activity assay. Chondrocytes treated with IL1β and the untreated control were subjected to the Rac1 activity assay. Chondrocytes transfected with CA-Rac1, DN-Rac1 or GFP were cultured under conditions for inducing calcification. To evaluate the effect of Rac1 in OA development, an OA model was created by anterior cruciate ligament transection in mice. CA-Rac1, DN-Rac1 and GFP lentivirus, or NSC23766, were injected intra-articularly. Joints were subjected to histological analysis. Results It was found that there is aberrant Rac1 activation in human OA cartilage. Rac1 activity could also be elevated by IL1β. Additionally, activated Rac1 promoted expression of MMP13, ADAMTS-5 and COLX by chondrocytes, partially through the β-catenin pathway. Moreover, activation of Rac1 in knee joints by CA-Rac1 lentivirus accelerated OA progression, while inhibition of Rac1 activity by DN-Rac1 lentivirus or Rac1 inhibitor NSC23766 delayed OA development. Therefore, we developed a strategy of controlled release of NSC23766 from chitosan microspheres to OA joints, which effectively protected cartilage from destruction. Conclusions These findings demonstrated that Rac1 activity is implicated in OA development. Also, controlled release of Rac1 inhibitor is a promising strategy for OA treatment.ISSN:0003-4967ISSN:1468-206