Role of Exosomal Non-Coding RNAs in Bone-Related Diseases

Abstract

Bone-related diseases seriously affect the lives of patients and carry a heavy economic burden on society. Treatment methods cannot meet the diverse clinical needs of affected patients. Exosomes participate in the occurrence and development of many diseases through intercellular communication, including bone-related diseases. Studies have shown that exosomes can take-up and “package” non-coding RNAs and “deliver” them to recipient cells, thereby regulating the function of recipient cells. The exosomal non-coding RNAs secreted by osteoblasts, osteoclasts, chondrocytes, and other cells are involved in the regulation of bone-related diseases by inhibiting osteoclasts, enhancing chondrocyte activity and promoting angiogenesis. Here, we summarize the role and therapeutic potential of exosomal non-coding RNAs in the bone-related diseases osteoporosis, osteoarthritis, and bone-fracture healing, and discuss the clinical application of exosomes in patients with bone-related diseases.

Osteoblasts-Derived Exosomal lncRNA-MALAT1 Promotes Osteoclastogenesis by Targeting the miR-124/NFATc1 Signaling Axis in Bone Marrow-Derived Macrophages

“…This finding led us to think that lncRNA-MALAT1 may be highly involved in the regulation of periodontitis-related physiological activities and the homeostasis in bone remodeling. Emerging studies showed that lncRNA is an essential active partner of osteogenic activity, 16 while the effect of lncRNA- OIP5-AS1, 17 Linc01133 18 and lncRNA-MALAT1 4 in osteogenic differentiation of osteoblasts and periodontal ligament stem cells have been reported. However, the role of lncRNA in osteoclastic differentiation has rarely been reported, while our results complemented the importance of lncRNA shuttled by osteoblasts exosome in bone remodeling, providing new possibilities for pathogenesis of periodontitis.…”

Differential Expression of Non-Coding RNAs in Stem Cell Development and Therapeutics of Bone Disorders

“…Exosomes with low molecular weight, small size, stable structure, less toxicity, and other characteristics are employed as “nano-medicine carriers” in tissue regeneration and/or disease treatment [ 100 , 101 ]. Importantly, ncRNAs are present in exosomes that perform diverse functions including bone remodeling and bone-related disease [ 102 ]. BMSCs, osteoclasts, osteoblasts, lymphocytes, and macrophages secrete exosomes that regulate bone metabolism [ 103 ].…”

“…In bone homeostasis, osteoblasts, osteoclasts, chondrocytes, and other cells secrete exosomal ncRNAs, which are involved in the regulation of bone-related diseases by inhibiting osteoclast differentiation, enhancing chondrocytosis, and promoting angiogenesis. Exosomal miRNAs secreted from MSCs exhibit potential regulatory effects on osteogenesis [ 102 ]. In humans, during BMSC osteogenic differentiation, the expression of exosomal miRNAs plays a regulatory role, and a low expression of miR-885-5p serves as a negative regulator by suppressing Wnt5 and RUNX2 [ 105 ].…”

“…Several studies reported that exosomal miR-30d-5p and miR-133b-3p might interfere with bone formation through the targeting gene RUNX2. However, miR-30d-5p and miR-133b-3p are highly expressed in the osteoblast-derived exosomal body ( Figure 2 ) [ 102 , 108 , 109 ].…”

“…Several exosomal miRNAs secreted by mineralized osteoblasts, like miR-667-3p, miR-874-3p, miR-6769b-5p, miR-7044-5p, and miR-7668-3p, are highly expressed, and capable of enhancing the osteogenic differentiation of osteoblast precursors. This has been achieved through the inhibition of AXIN1 expression and the promotion of β-catenin expression [ 102 , 114 ].…”