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Fibroblast growth factor 2 supports osteoblastic niche cells during hematopoietic homeostasis recovery after bone marrow suppression

DC Field Value Language
dc.contributor.authorYoon, Kyung-Ae-
dc.contributor.authorSon, YeonSung-
dc.contributor.authorChoi, Young-Jin-
dc.contributor.authorKim, Joo-Hyun-
dc.contributor.authorCho, Je-Yoel-
dc.date.accessioned2017-07-06T00:49:53Z-
dc.date.available2017-07-19T14:53:14Z-
dc.date.issued2017-06-29-
dc.identifier.citationCell Communication and Signaling, 15(1):25ko_KR
dc.identifier.issn1478-811X-
dc.identifier.urihttps://hdl.handle.net/10371/117770-
dc.description.abstractBackground
Hematopoietic stem cell (HSC) maintenance requires a specific microenvironment. HSC niches can be activated by tissue damaging chemotherapeutic drugs and various cell signaling molecules such as SDF-1 and FGF, which might also result in bone marrow stress. Recent research has insufficiently shown that endosteal osteolineage cells and other niche constituents recover after marrow injury.

Methods
We investigated the role of FGF2 in the osteoblastic niche cells during hematopoietic homeostasis recovery after bone marrow injury. Mice were treated with 5-fluorouracil (5FU) to eliminate actively cycling cells in the bone marrow. Primary osteoblasts were isolated and subjected to cell culture. Real-time PCR, western blot and immunohistochemical staining were performed to study niche-related genes, osteoblast markers, and FGF2 signaling. Proliferation rate were analyzed by marker gene Ki67 and colony formation assay. Also, osterix-positive osteoprogenitor cells were isolated by FACS from Osx-GFP-Cre mice after 5FU treatment, and subjected to RNA-sequencing and analyzed for Fgf receptors and niche markers.

Results
The endosteal osteolineage cells isolated from 5FU-treated mice showed increased expression of the niche-related genes Sdf-1, Jagged-1, Scf, N-cad, Angpt1 and Vcam-1 and the osteoblast marker genes Osx, Opn, Runx2, and Alp, indicating that BM stress upon 5FU treatment activated the osteoblastic niche. Endosteal osteoblast expanded from a single layer to several layers 3 and 6days after 5FU treatment. During the early recovery phase in 5FU-activated osteoblastic niches increased FGF2 expression and activated its downstream pERK. FGF2 treatment resulted in increased proliferation rate and the expression of niche marker genes in 5FU-activated osteoblastic niche cells. RNA-seq analysis in Osterix-positive osteoprogenitor cells isolated from 5FU-treated Osx-GFP mice showed significantly increased expression of Fgf receptors Fgfr1, 2 and 3. Although osteoblastic niche cells were damaged by 5FU treatment in the beginning, the increased number of OB layers in the recovery phase may be derived from resident osteoprogenitor cells by FGF2 activation under stress.

Conclusions
Taken together, FGF2 signaling can regulate osteoblastic niche cells to support HSC homeostasis in response to bone marrow damage.
ko_KR
dc.description.uri10.1186/s12964-017-0181-2-
dc.language.isoenko_KR
dc.publisherBioMed Centralko_KR
dc.subjectFGF2ko_KR
dc.subjectHematopoietic stem cellko_KR
dc.subjectNicheko_KR
dc.subjectOsteoblastko_KR
dc.subjectOsteoprogenitorko_KR
dc.titleFibroblast growth factor 2 supports osteoblastic niche cells during hematopoietic homeostasis recovery after bone marrow suppressionko_KR
dc.typeArticleko_KR
dc.contributor.AlternativeAuthor윤경애-
dc.contributor.AlternativeAuthor손연성-
dc.contributor.AlternativeAuthor최영진-
dc.contributor.AlternativeAuthor김주현-
dc.contributor.AlternativeAuthor조제열-
dc.language.rfc3066en-
dc.rights.holderThe Author(s).-
dc.date.updated2017-07-02T03:21:45Z-
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