title: Transforming growth factor-beta1 inhibits tissue engineering cartilage absorption via inducing the generation of regulatory T cells.
abstract: The objective of the present study was to explore the mechanisms of transforming growth factor (TGF)-β1 inhibiting the absorption of tissue engineering cartilage. We transfected TGF-β1 gene into bone marrow mesenchymal stem cells (BMMSCs) and co-cultured with interferon (IFN)-γ and tumour necrosis factor (TNF)-α and CD4(+) CD25(-) T lymphocytes. We then characterized the morphological changes, apoptosis and characterization of chondrogenic-committed cells from TGF-β1(+) BMMSCs and explored their mechanisms. Results showed that BMMSCs apoptosis and tissue engineering cartilage absorption in the group with added IFN-γ and TNF-α were greater than in the control group. In contrast, there was little BMMSC apoptosis and absorption by tissue engineering cartilage in the group with added CD4(+) CD25(-) T lymphocytes; Foxp3(+) T cells and CD25(+) CD39(+) T cells were found. In contrast, no type II collagen or Foxp3(+) T cells or CD25(+) CD39(+) T cells was found in the TGF-β1(-) BMMSC group. The data suggest that IFN-γ and TNF-α induced BMMSCs apoptosis and absorption of tissue engineering cartilage, but the newborn regulatory T (Treg) cells inhibited the function of IFN-γ and TNF-α and protected BMMSCs and tissue engineering cartilage. TGF-β1not only played a cartilage inductive role, but also inhibited the absorption of tissue engineering cartilage. The pathway proposed in our study may simulate the actual reaction procedure after implantation of BMMSCs and tissue engineering cartilage in vivo.
authors.affiliation: Department of Stomatology, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai, 200032, PR China.
authors.forename: Chichi
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Stomatology, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai, 200032, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Bi
authors.affiliation: Department of Stomatology, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai, 200032, PR China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Department of Stomatology, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai, 200032, PR China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Ding
authors.affiliation: Department of Stomatology, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai, 200032, PR China.
authors.forename: Xuehua
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Stomatology, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai, 200032, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhi Zao Ju Road, Shanghai, 200011, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cui
authors.affiliation: Department of Stomatology, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai, 200032, PR China.
authors.forename: Youcheng
authors.initials: Y
authors.lastname: Yu
mesh_terms: D065567:Absorption, Physiological; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D002356:Cartilage / Q000378:metabolism*; D019070:Cell Lineage; D048430:Cell Shape; D020219:Chondrogenesis; D053938:DNA Fragmentation; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D020287:In Situ Nick-End Labeling; D007371:Interferon-gamma / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*; D023822:Tissue Engineering / Q000379:methods*; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D018076:DNA, Complementary; D053773:Transforming Growth Factor beta1; D007371:Interferon-gamma
keywords: bone marrow mesenchymal stem cells; chondrocytes; newborn regulatory T (Treg) cells; transforming growth factor-β1