2. Academic Validation
  3. Osteocytes/Osteoblasts Produce SAA3 to Regulate Hepatic Metabolism of Cholesterol

Osteocytes/Osteoblasts Produce SAA3 to Regulate Hepatic Metabolism of Cholesterol

  • Adv Sci (Weinh). 2024 Apr 13:e2307818. doi: 10.1002/advs.202307818.
Shijiang Huang 1,  Yuanjun Jiang 1,  Jing Li 2,  Linlin Mao 1,  Zeyou Qiu 3 4,  Sheng Zhang 1,  Yuhui Jiang 1,  Yong Liu 1,  Wen Liu 1,  Zhi Xiong 1,  Wuju Zhang 1 5,  Xiaolin Liu 1,  Yue Zhang 1,  Xiaochun Bai 1 6,  Bin Guo 1 7
Affiliations

Affiliations

  • 1 State Key Laboratory of Organ Failure Research, Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China.
  • 2 Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
  • 3 Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China.
  • 4 Equipment Material Department, West China Xiamen Hospital of Sichuan University, Xiamen, Fujian, 361000, China.
  • 5 Central Laboratory, The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, 510900, China.
  • 6 Guangdong Provincial Key Laboratory of Bone and Joint Degenerative Diseases, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, 510630, China.
  • 7 The Tenth Affiliated Hospital, Southern Medical University, Dongguan, Guangdong, 523018, China.
PMID: 38613835 DOI: 10.1002/advs.202307818
Abstract

Hypercholesterolaemia is a systemic Metabolic Disease, but the role of organs other than liver in Cholesterol metabolism is unappreciated. The phenotypic characterization of the Tsc1Dmp1 mice reveal that genetic depletion of tuberous sclerosis complex 1 (TSC1) in osteocytes/osteoblasts (Dmp1-Cre) triggers progressive increase in serum Cholesterol level. The resulting Cholesterol metabolic dysregulation is shown to be associated with upregulation and elevation of serum amyloid A3 (SAA3), a lipid metabolism related factor, in the bone and serum respectively. SAA3, elicited from the bone, bound to Toll-like Receptor 4 (TLR4) on hepatocytes to phosphorylate c-Jun, and caused impeded conversion of Cholesterol to bile acids via suppression on Cholesterol 7 α-hydroxylase (Cyp7a1) expression. Ablation of Saa3 in Tsc1Dmp1 mice prevented the CYP7A1 reduction in liver and Cholesterol elevation in serum. These results expand the understanding of bone function and hepatic regulation of Cholesterol metabolism and uncover a potential therapeutic use of pharmacological modulation of SAA3 in hypercholesterolaemia.

Keywords

CYP7A1; SAA3; bone‐liver crosstalk; hypercholesterolaemia; osteocytes/osteoblasts.

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