Different impact of short-term and long-term hindlimb disuse on bone homeostasis.

Disuse osteoporosis is one of the major problems of bone health which commonly occurs in astronauts during long-term spaceflight and bedridden patients. However, the mechanisms underlying such mechanical unloading induced bone loss have not been fully understood. In this study, we employed hindlimb-unloading mice models with different length of tail suspension to investigate if the bone loss was regulated by distinct factors under different duration of disuse. Our micro-CT results showed more significant decrease of bone mass in 6W (6-week) tail-suspension mice compared to the 1W (1-week) tail-suspension ones, as indicated by greater reduction of BV/TV, Tb.N, B.Ar/T.Ar and Ct.Th. RNA-sequencing results showed significant effects of hindlimb disuse on cell locomotion and immune system process which could cause bone loss.Real-time quantitative PCR results indicated a greater number of bone formation related genes that were downregulated in short-term tail-suspension mice compared to the long-term ones. It is, thus, suggested while sustained hindlimb unloading continuously contributes to bone loss, molecular regulation of bone homeostasis tends to reach a balance during this process.

Distinct differences between calvarial and long bone osteocytes in cell morphologies, gene expression and aging responses.

Osteocytes are the terminally differentiated bone cells resulted from bone formation. Although there are two distinct processes of bone formation, intramembranous and endochondral ossifications contributing to the formation of calvarial and long bones, it is not clear whether the distinct pathways determine the differences between calvaria and femoral cortical bone derived osteocytes. In the present study, we employed confocal structured illumination microscopy and mRNA-sequencing analysis to characterize the morphologic and transcriptomic expression of osteocytes from murine calvaria and mid-shaft femoral cortical bone. Structured illumination microscopy and geometric modelling showed round shaped and irregularly scattered calvarial osteocytes compared to spindle shaped and orderly arrayed cortical osteocytes. mRNA-sequencing analysis indicated different transcriptomic profiles between calvarial and cortical osteocytes and provided evidence that mechanical response of osteocytes may contribute to geometrical differences. Furthermore, transcriptomic analysis showed that these two groups of osteocytes come from distinct pathways with 121 ossification-related genes differentially expressed. Analysis of correlation between ossification and osteocyte geometries via a Venn diagram showed that several genes related to ossification, cytoskeleton organization and dendrite development were differentially expressed between calvarial and cortical osteocytes. Finally, we demonstrated that aging disrupted the organization of dendrites and cortical osteocytes but had no significant effects on calvarial osteocytes. Together, we conclude that calvarial and cortical osteocytes are different in various aspects, which is probably the consequence of their distinct pathways of ossification.

Erratum: Author Correction: Exosomes-the enigmatic regulators of bone homeostasis.

[This corrects the article DOI: 10.1038/s41413-018-0039-2.].

Exosomes-the enigmatic regulators of bone homeostasis.

Exosomes are a heterogeneous group of cell-derived membranous structures, which mediate crosstalk interaction between cells. Recent studies have revealed a close relationship between exosomes and bone homeostasis. It is suggested that bone cells can spontaneously secret exosomes containing proteins, lipids and nucleic acids, which then to regulate osteoclastogenesis and osteogenesis. However, the network of regulatory activities of exosomes in bone homeostasis as well as their therapeutic potential in bone injury remain largely unknown. This review will detail and discuss the characteristics of exosomes, the regulatory activities of exosomes in bone homeostasis as well as the clinical potential of exosomes in bone injury.