期刊
LIFE SCIENCES
卷 310, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2022.121073
关键词
Low-density lipoprotein receptor; Bone microstructure; Osteoclastogenesis; c-fos; NFATc1
资金
- Scientific and Technological Innovation Action Plan of the Shanghai Natural Science Foundation [20ZR1409100]
- Chinese Association of Integration of Traditional and Western Medicine special foundation for Obstetrics and Gynecology-PuZheng Pharmaceutical Foundation [FCK-PZ-08]
- Shanghai Hospital Association [X2021046]
- Special Foundation for Healthcare Research of the Shanghai Municipal Health Commission [202150042]
LDLR deficiency results in reduced bone mineral density of the tibial cancellous bone and promotes osteoclastogenesis. However, LDLR deficiency does not have a significant impact on the number of osteoblasts, and 17 beta-estradiol can inhibit osteoclastogenesis in vitro.
Aim: The low-density lipoprotein receptor (LDLR) plays a crucial role in regulating lipid metabolism. However, whether LDLR deficiency affects bone mass and morphology remains controversial. This study aimed to analyze the bone phenotypes of LDLR knockout (LDLR-/-) mice. Main methods: Eight-week-old LDLR-/- and wild-type (WT) mice were subjected to microcomputed tomography to detect bone phenotypes. Enzyme-linked immunosorbent assay kits were used to detect the serum estrogen levels and matrix metalloproteinase 9 (MMP-9) levels in tissue homogenates. Von Kossa, toluidine blue, tartrate-resistant acid phosphatase (TRAP) staining, and calcein labeling were performed to explore bone turnover parameters. In vitro, osteoclastogenesis was induced in bone marrow cells from LDLR-/- mice and WT mice in the presence or absence of 17 beta-estradiol. The microphotographs and number of osteoclasts were validated using TRAP staining. Relative gene expression during osteoclast differentiation and maturation was determined by quantitative real-time polymerase chain reaction. Key findings: LDLR deficiency results in reduced bone mineral density of the tibial cancellous bone, indicating bone loss to some extent in LDLR-/- mice. LDLR deficiency significantly increased the number of osteoclasts, but not osteoblasts. In vitro, bone marrow cells from LDLR-/- mice displayed enhanced osteoclastic potential along with increased expression of TRAP, cathepsin K, nuclear factor of activated T-cells 1 (NFATc1), c-fos, and MMP-9 and inhibited dendritic cell-specific transmembrane protein expression. Moreover, 17 beta-estradiol treatment can inhibit osteoclastogenesis in vitro. Significance: Our data demonstrated that LDLR deficiency promoted osteoclastogenesis by upregulating c-fos and NFATc1 expression, reducing cancellous bone mass in LDLR-/- mice.
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