Microfibrillar-associated Protein 5 Suppresses Adipogenesis by Inhibiting Essential Coactivator of PPARγ

Overview

Journal Sci Rep

Specialty Science

Date 2023 Apr 5

PMID 37020143

Authors

Tianlong Zhang

Haoran Li

Shiwei Sun

Wuling Zhou

Tieqi Zhang

Yueming Yu

Qiang Wang

Minghai Wang

Affiliations

Soon will be listed here.

Abstract

Femoral head necrosis is responsible for severe pain and its incidence is increasing. Abnormal adipogenic differentiation and fat cell hypertrophy of bone marrow mesenchymal stem cells increase intramedullary cavity pressure, leading to osteonecrosis. By analyzing gene expression before and after adipogenic differentiation, we found that Microfibril-Associated Protein 5 (MFAP5) is significantly down-regulated in adipogenesis whilst the mechanism of MFAP5 in regulating the differentiation of bone marrow mesenchymal stem cells is unknown. The purpose of this study was to clarify the role of MAFP5 in adipogenesis and therefore provide a theoretical basis for future therapeutic options of osteonecrosis. By knockdown or overexpression of MFAP5 in C3H10 and 3T3-L1 cells, we found that MFAP5 was significantly down-regulated as a key regulator of adipogenic differentiation, and identified the underlying downstream molecular mechanism. MFAP5 directly bound to and inhibited the expression of Staphylococcal Nuclease And Tudor Domain Containing 1, an essential coactivator of PPARγ, exerting an important regulatory role in adipogenesis.

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References

Di Leo L, Vegliante R, Ciccarone F, Salvatori I, Scimeca M, Bonanno E . Forcing ATGL expression in hepatocarcinoma cells imposes glycolytic rewiring through PPAR-α/p300-mediated acetylation of p53. Oncogene. 2018; 38(11):1860-1875. PMC: 6756110. DOI: 10.1038/s41388-018-0545-0. View

Jiang Y, Zhang Y, Zhang H, Zhu B, Li P, Lu C . Pravastatin prevents steroid-induced osteonecrosis in rats by suppressing PPARγ expression and activating Wnt signaling pathway. Exp Biol Med (Maywood). 2014; 239(3):347-55. DOI: 10.1177/1535370213519215. View

Li Q, Peng H, Fan H, Zou X, Liu Q, Zhang Y . The LIM protein Ajuba promotes adipogenesis by enhancing PPARγ and p300/CBP interaction. Cell Death Differ. 2015; 23(1):158-68. PMC: 4815986. DOI: 10.1038/cdd.2015.83. View

Hashimoto Y, Matsuzaki E, Higashi K, Takahashi-Yanaga F, Takano A, Hirata M . Sphingosine-1-phosphate inhibits differentiation of C3H10T1/2 cells into adipocyte. Mol Cell Biochem. 2014; 401(1-2):39-47. DOI: 10.1007/s11010-014-2290-1. View

Ambrosi T, Scialdone A, Graja A, Gohlke S, Jank A, Bocian C . Adipocyte Accumulation in the Bone Marrow during Obesity and Aging Impairs Stem Cell-Based Hematopoietic and Bone Regeneration. Cell Stem Cell. 2017; 20(6):771-784.e6. PMC: 5459794. DOI: 10.1016/j.stem.2017.02.009. View

Combs M, Knutsen R, Broekelmann T, Toennies H, Brett T, Miller C . Microfibril-associated glycoprotein 2 (MAGP2) loss of function has pleiotropic effects in vivo. J Biol Chem. 2013; 288(40):28869-80. PMC: 3789982. DOI: 10.1074/jbc.M113.497727. View

Duan Z, Zhao X, Fu X, Su C, Xin L, Saarikettu J . Tudor-SN, a novel coactivator of peroxisome proliferator-activated receptor γ protein, is essential for adipogenesis. J Biol Chem. 2014; 289(12):8364-74. PMC: 3961662. DOI: 10.1074/jbc.M113.523456. View

Warnke I, Goralczyk R, Fuhrer E, Schwager J . Dietary constituents reduce lipid accumulation in murine C3H10 T1/2 adipocytes: A novel fluorescent method to quantify fat droplets. Nutr Metab (Lond). 2011; 8(1):30. PMC: 3117678. DOI: 10.1186/1743-7075-8-30. View

Graneli C, Karlsson C, Brisby H, Lindahl A, Thomsen P . The effects of PPAR-γ inhibition on gene expression and the progression of induced osteogenic differentiation of human mesenchymal stem cells. Connect Tissue Res. 2014; 55(4):262-74. DOI: 10.3109/03008207.2014.910198. View

10.

Li H, Zhou W, Sun S, Zhang T, Zhang T, Huang H . Microfibrillar-associated protein 5 regulates osteogenic differentiation by modulating the Wnt/β-catenin and AMPK signaling pathways. Mol Med. 2021; 27(1):153. PMC: 8647299. DOI: 10.1186/s10020-021-00413-0. View

11.

Li J, Zhu X, Li F, Huang C, Huang X, Wang J . MFAP5 facilitates the aggressiveness of intrahepatic Cholangiocarcinoma by activating the Notch1 signaling pathway. J Exp Clin Cancer Res. 2019; 38(1):476. PMC: 6882185. DOI: 10.1186/s13046-019-1477-4. View

12.

Landgraeber S, Warwas S, Classen T, Jager M . Modifications to advanced Core decompression for treatment of Avascular necrosis of the femoral head. BMC Musculoskelet Disord. 2017; 18(1):479. PMC: 5698933. DOI: 10.1186/s12891-017-1811-y. View

13.

Chandra V, Huang P, Hamuro Y, Raghuram S, Wang Y, Burris T . Structure of the intact PPAR-gamma-RXR- nuclear receptor complex on DNA. Nature. 2008; 456(7220):350-6. PMC: 2743566. DOI: 10.1038/nature07413. View

14.

Mota de Sa P, Richard A, Hang H, Stephens J . Transcriptional Regulation of Adipogenesis. Compr Physiol. 2017; 7(2):635-674. DOI: 10.1002/cphy.c160022. View

15.

Miyanishi K, Yamamoto T, Irisa T, Yamashita A, Jingushi S, Noguchi Y . Bone marrow fat cell enlargement and a rise in intraosseous pressure in steroid-treated rabbits with osteonecrosis. Bone. 2002; 30(1):185-90. DOI: 10.1016/s8756-3282(01)00663-9. View

16.

Deng Q, Li P, Che M, Liu J, Biswas S, Ma G . Activation of hedgehog signaling in mesenchymal stem cells induces cartilage and bone tumor formation via Wnt/β-Catenin. Elife. 2019; 8. PMC: 6764825. DOI: 10.7554/eLife.50208. View

17.

Milwid J, Elman J, Li M, Shen K, Manrai A, Gabow A . Enriched protein screening of human bone marrow mesenchymal stromal cell secretions reveals MFAP5 and PENK as novel IL-10 modulators. Mol Ther. 2014; 22(5):999-1007. PMC: 4017089. DOI: 10.1038/mt.2014.17. View

18.

Ni Y, Ji C, Wang B, Qiu J, Wang J, Guo X . A Novel pro-adipogenesis factor abundant in adipose tissues and over-expressed in obesity acts upstream of PPARγ and C/EBPα. J Bioenerg Biomembr. 2012; 45(3):219-28. DOI: 10.1007/s10863-012-9492-6. View

19.

Nakashima Y, Nahar S, Miyagi-Shiohira C, Kinjo T, Toyoda Z, Kobayashi N . A Liquid Chromatography with Tandem Mass Spectrometry-Based Proteomic Analysis of the Proteins Secreted by Human Adipose-Derived Mesenchymal Stem Cells. Cell Transplant. 2018; 27(10):1469-1494. PMC: 6180722. DOI: 10.1177/0963689718795096. View

20.

Nolte R, Wisely G, Westin S, Cobb J, Lambert M, Kurokawa R . Ligand binding and co-activator assembly of the peroxisome proliferator-activated receptor-gamma. Nature. 1998; 395(6698):137-43. DOI: 10.1038/25931. View