Bone‐Adipose Tissue Crosstalk: Role of Adipose Tissue Derived Extracellular Vesicles in Bone Diseases

Abstract

Bone is a metabolically active organ that undergoes constant remodeling throughout life. A failure of this process leads to pathological destructive bone diseases such as osteoporosis, rheumatoid arthritis, and osteoarthritis. Studies of the interplay between adipose tissue and bone system, have revealed that adipose tissue disorders (e.g. obesity) strongly influence the development of bone diseases. Adipokines secreted by adipose tissue play important roles in the crosstalk between bone and adipose tissue. Recently, extracellular vesicles (EVs) have been identified as a novel method of communication between different organs and have attracted increased attention in the field of bone remodeling process. Adipokines carried by EVs are known to play pivotal roles in bone remodeling processes including osteogenesis and osteoclastogenesis. In this review, we highlighted the role of adipose tissue derived EVs (EVs-AT) in the context of bone remodeling events and focused on the characteristics of EVs-AT and their components in the regulation of bone diseases.Moreover, we introduced the intriguing therapeutic application of EVs-AT in different pathological destructive bone diseases and proposed future directions for research on EVs-AT in bone diseases.

Circulating Extracellular Vesicles and Particles Derived From Adipocytes: The Potential Role in Spreading MicroRNAs Associated With Cellular Senescence

“…In this context, it is possible to infer that miR-15b-5p, an upregulated miRNA in circulating adipocyte-derived EVPs here reported, can be involved with those findings of CCND1, given that this cyclin was strongly reduced in muscle stem cells from 20 to 22-months-old male mice, impairing myoblast proliferation and differentiation, including in response to regenerative conditions ( Brett et al, 2020 ). In addition, Zhang et al (2021) suggested the role of adipose tissue-derived EVPs cargo on bone remodeling events. Taken that tibia from 19-month-old aged female mice showed downregulated cyclins, CCNA2, CCND3, CCNE1-2, the upregulation of miRNA-15b-5p, miR-24-3p, and miR-92b-3p (and consequent silencing of cyclins) can be related, at least in part, to declines in bone mass and fracture in older adults, in the context of obesity.…”

“…Inhibition of E2F3 induced cell cycle arrest by inhibiting the induction of S phase (Leone et al, 1998). Moreover, bioinformatic analyses, functional clustering analysis, pathway enrichment, gene network interactions, and transcription factor of transcriptomic changes in tibia from old mice compared with young ones revealed "cell cycle" as a crucial category, including terms as organ development, cell cycle checkpoints and regulation of programmed cell death, chromatin assembly, DNA damage checkpoint, regulation of cell cycle, apoptosis, and regulation of metabolic process (Zhang et al, 2021). On the other hand, miRNA profiling in circulating EVPs can reflect the tissue and cellular miRNA signatures.…”

Adipose Stromal/Stem Cell-Derived Extracellular Vesicles: Potential Next-Generation Anti-Obesity Agents

“…Clearly, the therapeutic use of EVs from ASCs in the clinic is also attractive and scientifically supported by the results obtained through a wide variety of experimental pathological conditions, ranging from kidney transplantation to inflammatory bone diseases and tissue regeneration [94][95][96][97].…”

“…Furthermore, it must be considered that EVs carry only a fraction of the molecules produced by the cells of origin, which are selected for specific purposes such as supplying neighboring/distal cells with energetically, biochemically or enzymatically useful materials, as well as nucleic acids, which can alter the expression of the target genes. This can be an advantage but also as a disadvantage, considering the restriction in the range of products donated by EVs compared with entire MSCs [96], and also implies that the therapeutic dose and efficacy of EVs must still be clearly defined. Furthermore, EVs can home in on certain tissues depending on their source tissue, which would be mainly useful in the case of EV use for targeted drug delivery [33], although it is not clear how extensive this homing ability is.…”

The Role of Extracellular Vesicles in Osteoporosis: A Scoping Review

“…Kian F Eichholz et al demonstrated that osteocytes can be mechanically activated to secrete EVs to regulate mesenchymal stem cell differentiation [ 48 ]. EVs not only play a therapeutic role in other diseases, but also play an important role in osteoporosis [ 28 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ]. Based on Xin Qi et al, exosomes secreted by human-induced pluripotent stem cell-derived mesenchymal stem cells repair critical-sized bone defects through enhanced angiogenesis and osteogenesis in osteoporotic rats [ 57 ].…”