Irradiation Haematopoiesis Recovery Orchestrated by IL-12/IL-12Rβ1/TYK2/STAT3-Initiated Osteogenic Differentiation of Mouse Bone Marrow-Derived Mesenchymal Stem Cells

Overview

Journal Front Cell Dev Biol

Specialty Cell Biology

Date 2021 Sep 20

PMID 34540843

Citations 3

Authors

Fengjie Li

Rong Zhang

Changpeng Hu

Qian Ran

Yang Xiang

Lixin Xiang

Li Chen

Yang Yang

Shengwen Calvin Li

Gang Zhang

Zhongjun Li

Affiliations

Soon will be listed here.

Abstract

Purpose: 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 . 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.

Citing Articles

Interleukin-12 sustained release system promotes hematopoietic recovery after radiation injury.

Lin C, Xiang Y, Zhang Y, Yang Z, Chen N, Zhang W MedComm (2020). 2024; 5(9):e704.

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JAK-STAT signaling in inflammation and stress-related diseases: implications for therapeutic interventions.

Sarapultsev A, Gusev E, Komelkova M, Utepova I, Luo S, Hu D Mol Biomed. 2023; 4(1):40.

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TYK2 in Immune Responses and Treatment of Psoriasis.

Shang L, Cao J, Zhao S, Zhang J, He Y J Inflamm Res. 2022; 15:5373-5385.

PMID: 36147687 PMC: 9488612. DOI: 10.2147/JIR.S380686.

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