Abstract
The study aims to characterize functions of bone morphogenetic protein 2 (BMP2) gene in the process of subcutaneous (SQ) fat deposition of bovine, thereby providing insights into mechanisms for the use of BMP2 in fat management. Our results show that BMP2 was extensively expressed in bovine and relatively rich in adipose tissue. Exogenous BMP2 significantly enhanced proliferation of bovine preadipocytes. Consistently, si-BMP2 apparently induced cell cycle arrest at G0/G1 phase and decreased proliferation of preadipocytes. Meanwhile, exogenous BMP2 mildly enhanced preadipocyte differentiation at day 3 of differentiation, as evidenced by accelerated lipid accumulation, as well as increased mRNA and protein expressions of adipogenic key transcription factor PPARγ; contrary results about lipids were found by BMP2 interference treatment. No difference was observed concerning BMP2 or si-BMP2 treatment at day − 2 and day 0 of differentiation. Additionally, LDN-193189 (inhibitor of BMP type I receptor) pretreatment diminished the enhancement of preadipocyte proliferation and differentiation induced by BMP2, as evidenced by constant proliferation rate and PPARγ expressions. Furthermore, BMP2 markedly enhanced phosphorylation level of SMAD1/5/9, and LDN-193189 could diminish the difference caused by BMP2. Thus, our results suggest that BMP2 triggers BMP/SMAD signaling pathway, promoting both hyperplasia and hypertrophy of bovine preadipocytes.
Similar content being viewed by others
References
Barboza E, Caula A, Machado F (1999) Potential of recombinant human bone morphogenetic protein-2 in bone regeneration. Implant Dent 8:360–367. https://doi.org/10.1097/00008505-199904000-00006
Cristancho AG, Lazar MA (2011) Forming functional fat: a growing understanding of adipocyte differentiation. Nat Rev Mol Cell Biol 12:722–734. https://doi.org/10.1038/nrm3198
Denton NF, Eghleilib M, Al-Sharifi S, Todorcevic M, Neville MJ, Loh N et al (2019) Correction to: Bone morphogenetic protein 2 is a depot-specific regulator of human adipogenesis. Int J Obes (lond) 43:2593. https://doi.org/10.1038/s41366-019-0475-0
Dodson MV, Allen RE, Du M, Bergen WG, Velleman SG, Poulos SP et al (2015) INVITED REVIEW: Evolution of meat animal growth research during the past 50 years: adipose and muscle stem cells. J Anim Sci 93:457–481. https://doi.org/10.2527/jas.2014-8221
Dodson MV, Hausman GJ, Guan L, Du M, Rasmussen TP, Poulos SP et al (2010) Lipid metabolism, adipocyte depot physiology and utilization of meat animals as experimental models for metabolic research. Int J Biol Sci 6:691–699. https://doi.org/10.7150/ijbs.6.691
Fukuda T, Fukuda R, Koinuma D, Moustakas A, Miyazono K, Heldin CH (2021) BMP2-induction of FN14 promotes protumorigenic signaling in gynecologic cancer cells. Cell Signal 87:110146. https://doi.org/10.1016/j.cellsig.2021.110146
Hata K, Nishimura R, Ikeda F, Yamashita K, Matsubara T, Nokubi T et al (2003) Differential roles of Smad1 and p38 kinase in regulation of peroxisome proliferator-activating receptor gamma during bone morphogenetic protein 2-induced adipogenesis. Mol Biol Cell 14:545–555. https://doi.org/10.1091/mbc.e02-06-0356
Hausman GJ, Basu U, Wei S, Hausman DB, Dodson MV (2014) Preadipocyte and adipose tissue differentiation in meat animals: influence of species and anatomical location. Annu Rev Anim Biosci 2:323–351. https://doi.org/10.1146/annurev-animal-022513-114211
Hausman GJ, Dodson MV, Ajuwon K, Azain M, Barnes KM, Guan LL et al (2009) Board-invited review: the biology and regulation of preadipocytes and adipocytes in meat animals. J Anim Sci 87:1218–1246. https://doi.org/10.2527/jas.2008-1427
Heldin CH, Moustakas A (2016) Signaling receptors for TGF-β family members. Cold Spring Harb Perspect Biol 8(8):a022053. https://doi.org/10.1101/cshperspect.a022053
Huang H, Song TJ, Li X, Hu L, He Q, Liu M et al (2009) BMP signaling pathway is required for commitment of C3H10T1/2 pluripotent stem cells to the adipocyte lineage. Proc Natl Acad Sci U S A 106:12670–12675. https://doi.org/10.1073/pnas.0906266106
Jo J, Gavrilova O, Pack S, Jou W, Mullen S, Sumner AE et al (2009) Hypertrophy and/or hyperplasia: dynamics of adipose tissue growth. PLoS Comput Biol 5:e1000324. https://doi.org/10.1371/journal.pcbi.1000324
Kloting N, Bluher M (2014) Adipocyte dysfunction, inflammation and metabolic syndrome. Rev Endocr Metab Disord 15:277–287. https://doi.org/10.1007/s11154-014-9301-0
Lee MJ (2018) Transforming growth factor beta superfamily regulation of adipose tissue biology in obesity. Biochim Biophys Acta Mol Basis Dis 1864:1160–1171. https://doi.org/10.1016/j.bbadis.2018.01.025
Lee SY, Lee JH, Kim JY, Bae YC, Suh KT, Jung JS (2014) BMP2 increases adipogenic differentiation in the presence of dexamethasone, which is inhibited by the treatment of TNF-alpha in human adipose tissue-derived stromal cells. Cell Physiol Biochem 34:1339–1350. https://doi.org/10.1159/000366341
Lee VR, Barr KJ, Kelly JJ, Johnston D, Brown CFC, Robb KP et al (2018) Pannexin 1 regulates adipose stromal cell differentiation and fat accumulation. Sci Rep 8:16166. https://doi.org/10.1038/s41598-018-34234-9
Margoni A, Fotis L, Papavassiliou AG (2012) The transforming growth factor-beta/bone morphogenetic protein signalling pathway in adipogenesis. Int J Biochem Cell Biol 44:475–479. https://doi.org/10.1016/j.biocel.2011.12.014
Massagué J, Wotton D (2000) Transcriptional control by the TGF-beta/Smad signaling system. EMBO J 19:1745–1754. https://doi.org/10.1093/emboj/19.8.1745
Nohe A, Hassel S, Ehrlich M, Neubauer F, Sebald W, Henis YI et al (2002) The mode of bone morphogenetic protein (BMP) receptor oligomerization determines different BMP-2 signaling pathways. J Biol Chem 277:5330–5338. https://doi.org/10.1074/jbc.M102750200
Schleinitz D, Bottcher Y, Bluher M, Kovacs P (2014) The genetics of fat distribution. Diabetologia 57:1276–1286. https://doi.org/10.1007/s00125-014-3214-z
Skillington J, Choy L, Derynck R (2002) Bone morphogenetic protein and retinoic acid signaling cooperate to induce osteoblast differentiation of preadipocytes. J Cell Biol 159:135–146. https://doi.org/10.1083/jcb.200204060
Sottile V, Seuwen K (2000) Bone morphogenetic protein-2 stimulates adipogenic differentiation of mesenchymal precursor cells in synergy with BRL 49653 (rosiglitazone). FEBS Lett 475:201–204. https://doi.org/10.1016/s0014-5793(00)01655-0
Vanhatupa S, Ojansivu M, Autio R, Juntunen M, Miettinen S (2015) Bone morphogenetic protein-2 induces donor-dependent osteogenic and adipogenic differentiation in human adipose stem cells. Stem Cells Transl Med 4:1391–1402. https://doi.org/10.5966/sctm.2015-0042
Wang MH, Zhou XM, Zhang MY, Shi L, Xiao RW, Zeng LS et al. (2017) BMP2 promotes proliferation and invasion of nasopharyngeal carcinoma cells via mTORC1 pathway. Aging (Albany NY) 9: 1326–1340. https://doi.org/10.18632/aging.101230.
Wang S, Zhou G, Shu G, Wang L, Zhu X, Gao P et al (2013) Glucose utilization, lipid metabolism and BMP-Smad signaling pathway of porcine intramuscular preadipocytes compared with subcutaneous preadipocytes. Cell Physiol Biochem 31:981–996. https://doi.org/10.1159/000350116
Wei S, Fu X, Liang X, Zhu MJ, Jiang Z, Parish SM et al (2015) Enhanced mitogenesis in stromal vascular cells derived from subcutaneous adipose tissue of Wagyu compared with those of Angus cattle. J Anim Sci 93:1015–1024. https://doi.org/10.2527/jas.2014-7923
Wei S, Zhang L, Zhou X, Du M, Jiang Z, Hausman GJ et al (2013) Emerging roles of zinc finger proteins in regulating adipogenesis. Cell Mol Life Sci 70:4569–4584. https://doi.org/10.1007/s00018-013-1395-0
Wei S, Zhang M, Zheng Y, Yan P (2018a) ZBTB16 overexpression enhances white adipogenesis and induces brown-like adipocyte formation of bovine white intramuscular preadipocytes. Cell Physiol Biochem 48:2528–2538. https://doi.org/10.1159/000492697
Wei S, Zheng Y, Zhang M, Zheng H, Yan P (2018b) Grape seed procyanidin extract inhibits adipogenesis and stimulates lipolysis of porcine adipocytes in vitro. J Anim Sci 96:2753–2762. https://doi.org/10.1093/jas/sky158
Funding
This project was supported by the Fundamental Research Funds for the Central Universities of China (KYYJ202102), the Jiangsu Agricultural Science and Technology Innovation Fund (CX(21)3136), and the National Natural Science Foundation of China (31501930).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare no competing interests.
Rights and permissions
About this article
Cite this article
Yang, L., Hao, W., Wang, H. et al. BMP2 increases hyperplasia and hypertrophy of bovine subcutaneous preadipocytes via BMP/SMAD signaling. In Vitro Cell.Dev.Biol.-Animal 58, 210–219 (2022). https://doi.org/10.1007/s11626-022-00661-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11626-022-00661-2