Exosomes derived from preadipocytes improve osteogenic differentiation, potentially via reduced miR‑223 expression

Abstract

Insufficient bone volume remains a key issue when using dental implants. Adipose tissue-derived stem cells (ADSCs) can accelerate bone healing when combined with dental implants. To improve the application of ADSCs for dental uses, the present study aimed to identify optimal implantation conditions. Mesenchymal stem cell-derived exosomes can induce naïve stem cells to differentiate through the osteogenic lineage. In the present study, exosomes derived from 3T3L1 preadipocytes (3T3L1-exo) were purified and characterized. The effects and potential mechanisms of 3T3L1-exo on 3T3L1 cell ossification were examined by reverse transcription-quantitative polymerase chain reaction, western blotting, electron microscopy, RNA sequencing and histological analysis. The current study confirmed that 3T3L1-exo enhanced 3T3L1 preadipocyte osteogenic differentiation, as revealed by upregulation of osteogenic differentiation-associated genes and increased Alizarin Red staining. Furthermore, the microRNA (miR) expression profiles of 3T3L1-exo and 3T3L1 preadipocytes were sequenced and compared. The results of a further analysis demonstrated that miR-223 expression was reduced in 3T3L1 preadipocytes stimulated by 3T3L1-exo compared with in unstimulated cells. This finding suggested that 3T3L1-exo promoted 3T3L1 bone formation by decreasing miR-223 through a competitive mechanism, another miRNA, or another factor. The mechanism by which miR-223 is decreased warrants further investigation. In conclusion, the application of 3T3L1-exo may be useful for investigating preadipocyte-induced bone regeneration.

Application of Adipose Tissue Stem Cells in Regenerative Dentistry

“…Finally, 33 original studies were reviewed. [ 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 ]…”

“…a. Types of studies : Of the 33 included studies, 23 involved the animal models[ 4 5 6 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 ] whereas three trials were done on humans[ 7 29 , 30 ] and seven studies were conducted in vitro [ 31 32 33 34 35 36 37 ] [ Table 1 ].…”

“…[ 4 5 6 9 10 11 12 13 14 15 , 18 19 20 21 22 24 25 26 , 32 34 ] Some studies obtained ADSCs from human liposuction aspirates, infrapatellar or BFP, and commercial cell lines. [ 7 17 , 23 27 , 29 30 , 37 ]…”

The Role of Exosomes in Bone Remodeling: Implications for Bone Physiology and Disease

“…More specifically, adipocytes deliver to MSCs RNA transcripts (of PPARγ , CEBPα , and CEBPδ ) and miRNAs (miR-138, miR30c, miR125a, miR-125b, and miR-31) that target the transcripts of osteogenic genes ( Runx2 , Osterix , Smad2 , and Smad4) and cause downregulation of osteocalcin (OSC) and osteopontin, all indications of an antiosteogenic impact [61]. Preadipocytes may favor each other's osteogenic differentiation through the exchange of exosomes which downregulate miR-223 in the recipient cell [62]. Exosomes from sinus mucosa cells, which line the osseous cavities, also promote osteoblastic differentiation and bone regeneration in vitro and in vivo [63].…”

Osteogenically-induced exosomes stimulate osteogenesis of human adipose-derived stem cells

“…To date, bone grafting is considered as the “gold standard” for treatment of bone defects, including autologous bone grafts, allogeneic bone grafts, and bone-graft substitutes (Dimitriou et al 2011 ). However, all these techniques have certain limitations, such as donor-site defect, poor bone quality and limited availability of grafting material (Du et al 2019 ; Lord et al 1988 ).…”