In:
Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 9 ( 2021-9-3)
Abstract:
Repairing the irradiation-induced osteogenic differentiation injury of bone marrow mesenchymal stem cells (BM-MSCs) is beneficial to recovering haematopoiesis injury in radiotherapy; however, its mechanism is elusive. Our study aimed to help meet the needs of understanding the effects of radiotherapy on BM-MSC osteogenic potential. Methods and Materials Balb/c mice and the BM-MSCs were used to evaluate the irradiation-induced osteogenic differentiation injury in vivo . The cellular and molecular characterization were applied to determine the mechanism for recovery of irradiation-derived haematopoiesis injuries. Results We report a functional role of IL-12 in acute irradiation hematopoietic injury recovery and intend to dissect the possible mechanisms through BM-MSC, other than the direct effect of IL-12 on hematopoietic stem and progenitor cells (HSPCs). Specifically, we show that early use of IL-12 enhanced the osteogenic differentiation of BM-MSCs through IL-12Rβ1/TYK2/STAT3 signaling; furthermore, IL-12 induced osteogenesis facilitated bone formation and irradiation hematopoiesis recovery when transplanted BM-MSCs in the femur of Balb/c mice. For the mechanism of action, we found that IL-12 receptor beta 1 (IL-12Rβ1) expression of irradiated BM-MSCs was upregulated rapidly, coincidentally consistent with early use of IL-12 induced osteogenic differentiation enhancement. IL-12Rβ1 and tyrosine kinase 2 gene (Tyk2) silencing experiments and phosphotyrosine of signal transducer and activator of transcription 3 (p-STAT3) suppression experiments indicated the IL-12Rβ1/TYK2/STAT3 signaling was essential in IL-12-induced osteogenic differentiation enhancement of BM-MSCs. Conclusion These findings suggested that IL-12 may exert BM-MSCs-based hematopoietic recovery by repairing osteogenic differentiation abilities damages through IL-12Rβ1/TYK2/STAT3 signaling pathway post-irradiation.
Type of Medium:
Online Resource
ISSN:
2296-634X
DOI:
10.3389/fcell.2021.729293
DOI:
10.3389/fcell.2021.729293.s001
DOI:
10.3389/fcell.2021.729293.s002
DOI:
10.3389/fcell.2021.729293.s003
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2021
detail.hit.zdb_id:
2737824-X
