CoCl <subscript>2</subscript> -simulated hypoxia potentiates the osteogenic differentiation of fibroblasts derived from tympanosclerosis by upregulating the expression of BMP-2. - OpacWWW

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Tytuł:: CoCl 2 -simulated hypoxia potentiates the osteogenic differentiation of fibroblasts derived from tympanosclerosis by upregulating the expression of BMP-2.
Autorzy:: Zhang C; ENT Institute and Department of Otolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, China.
Liu YW; ENT Institute and Department of Otolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, China.; NHC Key Laboratory of Hearing Medicine, Fudan University, Shanghai, PR China.
Chen M; ENT Institute and Department of Otolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, China.; NHC Key Laboratory of Hearing Medicine, Fudan University, Shanghai, PR China.
Min S; ENT Institute and Department of Otolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, China.; NHC Key Laboratory of Hearing Medicine, Fudan University, Shanghai, PR China.
Mao J; ENT Institute and Department of Otolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, China.; NHC Key Laboratory of Hearing Medicine, Fudan University, Shanghai, PR China.
Li Q; Stomatology Department, Eye & ENT Hospital, Fudan University, Shanghai, China.
Chi Z; ENT Institute and Department of Otolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, China.; NHC Key Laboratory of Hearing Medicine, Fudan University, Shanghai, PR China.
Źródło:: Cell biology international [Cell Biol Int] 2022 Sep; Vol. 46 (9), pp. 1423-1432. Date of Electronic Publication: 2022 Jul 10.
Typ publikacji:: Journal Article
Język:: English
Imprint Name(s):: Publication: 2013- : John Wiley & Sons Chichester :
Original Publication: London, UK : Published for the International Federation for Cell Biology by Academic Press, c1993-
MeSH Terms:: Bone Morphogenetic Protein 2*/metabolism
Myringosclerosis*/metabolism
Osteogenesis*
Cell Hypoxia/physiology ; Cells, Cultured ; Cobalt ; Fibroblasts/metabolism ; Fibrosis ; Humans ; Hypoxia/metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Vimentin/metabolism
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Grant Information:: 20174Y0062 Shanghai Municipal Health Bureau
Contributed Indexing:: Keywords: fibroblasts; hypoxia; ossification; tympanosclerosis
Substance Nomenclature:: 0 (BMP2 protein, human)
0 (Bone Morphogenetic Protein 2)
0 (HIF1A protein, human)
0 (Hypoxia-Inducible Factor 1, alpha Subunit)
0 (Vimentin)
3G0H8C9362 (Cobalt)
EVS87XF13W (cobaltous chloride)
Entry Date(s):: Date Created: 20220711 Date Completed: 20220805 Latest Revision: 20220809
Update Code:: 20240105
DOI:: 10.1002/cbin.11845
PMID:: 35811437
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Tympanosclerosis (TS) is a result of long-standing middle ear inflammation characterized by fibroblasts ossification. Fibrosis is the last revertible stage in the progress of middle ear inflammation to TS. It was hypothesized that chronic hypoxia could be modulating fibrosis, which in turn additionally further aggravated hypoxia via decreasing oxygen diffusion. However, the effects of hypoxia on osteoinductive activity of fibroblasts have not been explored. Herein, we purposed to explore the role of hypoxia in osteogenic differentiation of fibroblasts derived from TS. The expression of bone morphogenetic protein-2 (BMP-2), hypoxia-inducible factor-1α (HIF-1α), and Vimentin in the human surgical specimens of tympansclerosis was investigated by immunofluorescent staining. Furthermore, cultured fibroblasts were stratified into the following study groups: control, 25, 50, and 100 μM cobaltous chloride (CoCl 2 ) group. BMP-2, as well as HIF-1α levels of expression were detected via western blotting and immunofluorescence analysis. We found that the expression of BMP-2 and HIF-1α was significantly upregulated in TS tissues and these fibroblasts, which was vimentin positive surrounding sclerotic plaques, were also expressing HIF-1α positive. The results also demonstrated that CoCl 2 treatment increased nuclear HIF-1α protein level in the fibroblast. Furthermore, treatment with CoCl 2 significantly increased BMP-2 expression and remarkably elevated alkaline phosphatse activity and the mineralized nodules area. These data illustrate that hypoxia may play an osteogenic role in TS fibroblasts via the elevated expression of a possible osteogenic factor, BMP-2.
(© 2022 International Federation for Cell Biology.)

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CoCl 2 -simulated hypoxia potentiates the osteogenic differentiation of fibroblasts derived from tympanosclerosis by upregulating the expression of BMP-2.