P53 negatively regulates the osteogenic differentiation in jaw bone marrow MSCs derived from diabetic osteoporosis

Ying Zheng; Junhao Deng; Gang Wang; Xiaru Zhang; Lin Wang; Xiaocao Ma; Yawen Dai; Lingling E; Xiangwei Liu; Rong Zhang; Yi Zhang; Hongchen Liu

doi:10.1016/j.heliyon.2023.e15188

P53 negatively regulates the osteogenic differentiation in jaw bone marrow MSCs derived from diabetic osteoporosis

Heliyon. 2023 Apr 3;9(4):e15188. doi: 10.1016/j.heliyon.2023.e15188. eCollection 2023 Apr.

Authors

Ying Zheng^{1

2}, Junhao Deng³, Gang Wang^{1

2}, Xiaru Zhang⁴, Lin Wang^{1

2}, Xiaocao Ma², Yawen Dai^{1

2}, Lingling E², Xiangwei Liu^{1

2}, Rong Zhang², Yi Zhang⁴, Hongchen Liu^{1

2}

Affiliations

¹ Medical School of Chinese PLA, Beijing 100853, China.
² Institute of Stomatology & Oral Maxilla Facial Key Laboratory, Department of Stomatology, First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China.
³ Senior Department of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital, Beijing, 100048, China.
⁴ Department of Experimental Hematology and Biochemistry, Beijing Institute of Radiation Medicine, Beijing 100085, China.

Abstract

Patients with diabetic osteoporosis (DOP) often suffer from poor osseointegration of artificial implants, which is a challenge that affects implant outcomes. The osteogenic differentiation ability of human jaw bone marrow mesenchymal stem cells (JBMMSCs) is the key to implant osseointegration. Studies have shown that the microenvironment of hyperglycemia affects the osteogenic differentiation of mesenchymal stem cells (MSC), but the mechanism is still unclear. Therefore, the aim of this study was to isolate and culture JBMMSCs from surgically derived bone fragments from DOP patients and control patients to investigate the differences in their osteogenic differentiation ability and to elucidate its mechanisms. The results showed that the osteogenic ability of hJBMMSCs was significantly decreased in the DOP environment. Mechanism study showed that the expression of senescence marker gene P53 was significantly increased in DOP hJBMMSCs compared to control hJBMMSCs according to RNA-sequencing result. Further, DOP hJBMMSCs were found to display significant senescence using β-galactosidase staining, mitochondrial membrane potential and ROS assay, qRT-PCR and WB analysis. Overexpression of P53 in hJBMMSCs, knockdown of P53 in DOP hJBMMSCs, and knockdown followed by overexpression of P53 significantly affected the osteogenic differentiation ability of hJBMMSCs. These results suggest that MSC senescence is an important reason for decreasing osteogenic capacity in DOP patients. P53 is a key target in regulating hJBMMSCs aging, and knocking down P53 can effectively restore the osteogenic differentiation ability of DOP hJBMMSCs and promote osteosynthesis in DOP dental implants. It provided a new idea to elucidate the pathogenesis and treatment of diabetic bone metabolic diseases.

Keywords: Bone regeneration; Diabetic osteoporosis; Osteogenesis; Senescence; hJBMMSCs.