Effect of 3-phosphoinositide-dependent protein kinase 1 regulating osteoclasts on bone mineral density in osteoporotic mice

doi:10.12307/2021.168

Abstract

Abstract: BACKGROUND: Global researches on 3-phosphoinositide-dependent protein kinase 1 (PDK1) are mainly carried out in the fields of endocrine and oncology. There is no systematic research and report on whether the regulation of osteoclast improves osteoporosis in osteology.
OBJECTIVE: To explore the effect and molecular mechanism underlying the PDK1 regulation of osteoclasts in the pathogenesis of osteoporosis, so as to provide a new drug target for the clinical treatment of osteopenia.
METHODS: Osteoclasts were induced from whole bone marrow cells of PDK1 conditional knockout mice (PDK1-cKO) and wild-type mice. The induced osteoclasts were stained with tartrate-resistant acid phosphatase (TRAP), and the changes in the number and morphology of osteoclasts in the two groups were observed. Western blot assay was used to detect the expression of proteins related to regulation of osteoclast differentiation after PDK1 gene knockout. A mouse model of ovariectomy was established to observe the effect of PDK1 knockout on osteoporosis using Micro-CT scanning and TRAP-stained sections.
RESULTS AND CONCLUSION: TRAP staining results indicated that the number of osteoclasts with positive TRAP staining in the PDK1-cKO group was significantly reduced on the 4th and 6th days compared with the wild-type group (P < 0.05). Western blot results showed that the phosphorylation level of protein kinase B, a key protein regulating osteoclast differentiation, was decreased in the PDK1-cKO group (P < 0.05). After ovariectomy model was detected by Micro-CT scan in the two groups of mice, it was concluded by various metrological analyses that osteoporosis was significantly alleviated in the PDK1-cKO group compared with the wild-type group (P < 0.05). TRAP staining results revealed that TRAP-positive osteoclasts in the distal tibia of PDK1-cKO mice were significantly reduced compared with the wild-type group (P < 0.05). In conclusion, PDK1 gene can improve osteoporosis symptoms by regulating osteoclast differentiation and optimizing bone metabolism balance, which may be used as a drug target for the treatment of osteoporosis.

Key words: osteoporosis, osteoclasts, gene knockout, PDK1, mouse, tartrate-resistant acid phosphatase, bone remodeling

CLC Number:

Zhou Quan, Zhang Yanan, Bai Yiguang, Zhang Qiong, Nong Haibin, Liu Mingfu, Zeng Gaofeng, Zong Shaohui. Effect of 3-phosphoinositide-dependent protein kinase 1 regulating osteoclasts on bone mineral density in osteoporotic mice[J]. Chinese Journal of Tissue Engineering Research, 2021, 25(29): 4680-4684.

Figures/Tables 4

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