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Conditional knockout of the PDK‐1 gene in osteoblasts affects osteoblast differentiation and bone formation
Author(s) -
Bai Yiguang,
Zhang Qiong,
Chen Qiaoling,
Zhou Quan,
Zhang Yanan,
Shi Zhuohua,
g Haibin,
Liu Mingfu,
Zeng Gaofeng,
Zong Shaohui
Publication year - 2021
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.30249
Subject(s) - osteoblast , osteocalcin , protein kinase b , chemistry , endocrinology , medicine , alkaline phosphatase , conditional gene knockout , microbiology and biotechnology , phosphorylation , pi3k/akt/mtor pathway , signal transduction , biology , gene , biochemistry , phenotype , in vitro , enzyme
Abstract Osteoblasts are the main functional cells of bone formation, and they are responsible for the synthesis, secretion, and mineralization of the bone matrix. Phosphatidylinositol‐3‐kinase/Akt is an important signaling pathway involved in the regulation of cell proliferation, death, and survival. Some studies have shown that 3‐phosphoinositide‐dependent protein kinase‐1 ( PDK‐1 ) plays an important role in the phosphorylation of Akt. In the present study, an osteocalcin (OCN) promoter‐driven Cre‐LoxP system was established to specifically delete the PDK‐1 gene in osteoblasts. It was found that the size and weight of PDK‐1 conditional gene knockout (cKO) mice were significantly reduced. von Kossa staining and microcomputed tomography showed that the trabecular thickness, trabecular number, and bone volume were significantly decreased, whereas trabecular separation was increased, as compared with wide‐type littermates, which were characterized by a decreased bone mass. A model of distal femoral defect was established, and it was found that cKO mice delayed bone defect repair. In osteoblasts derived from PDK‐1 cKO mice, the alkaline phosphatase (ALP) secretion and ability of calcium mineralization were significantly decreased, and the expressions of osteoblast‐related proteins, runt‐related transcription factor 2, OCN, and ALP were also clearly decreased. Moreover, the phosphorylation level of Akt and downstream factor GSK3β and their response to insulin‐like growth factor‐1 (IGF‐1) decreased clearly. Therefore, we believe that PDK‐1 plays a very important role in osteoblast differentiation and bone formation by regulating the PDK‐1/Akt/GSK3β signaling pathway.