Dataset Information

Expression of Kielin/chordin-like protein is regulated by BMP-2 in osteoblasts.

ABSTRACT: Bone morphogenetic protein (BMP), an osteoinductive factor, is a cytokine that induces osteoblast differentiation and mineralization, and expected to be applicable for hard tissue reconstruction. Kielin/chordin-like protein (Kcp), a member of the family of cysteine-rich proteins, enhances BMP signaling. The present study found that expression of Kcp in osteoblasts was induced by BMP-2 in a concentration- and time-dependent manner. Up-regulation of Kcp by BMP-2 was inhibited by Dorsomorphin, a SMAD signaling inhibitor. The involvement of up-regulation of Kcp by BMP-2 in induction of osteoblast differentiation by BMP-2 was also examined, which showed that suppression of Kcp expression by si Kcp partially inhibited induction of osteoblast differentiation and mineralization by BMP-2. Together, these results suggest that Kcp induced by BMP-2 functions to provide positive feedback for promotion of osteoblastic differentiation and mineralization by BMP-2 in osteoblasts.

SUBMITTER: Toba K

PROVIDER: S-EPMC11321374 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature

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Expression of Kielin/chordin-like protein is regulated by BMP-2 in osteoblasts.

Toba Kazuki K Yamada Atsushi A Sasa Kiyohito K Shirota Tatsuo T Kamijo Ryutaro R

Bone reports 20240720

Bone morphogenetic protein (BMP), an osteoinductive factor, is a cytokine that induces osteoblast differentiation and mineralization, and expected to be applicable for hard tissue reconstruction. Kielin/chordin-like protein (Kcp), a member of the family of cysteine-rich proteins, enhances BMP signaling. The present study found that expression of <i>Kcp</i> in osteoblasts was induced by BMP-2 in a concentration- and time-dependent manner. Up-regulation of <i>Kcp</i> by BMP-2 was inhibited by Dors ...[more]

PMID: 39139593

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Project description:AimTo explore the functions of Chordin-like 2, which is encoded by CHRDL2, in the process of retinal pigmented epithelium (RPE) differentiation and damage repair.MethodsThe fetal RPE cells (fRPE) was obtained from aborted fetus which obeyed medical ethics. Real-time quantitative polymerase chain reaction was used to measure expression quantity of CHRDL2 and other functional genes expression. Knocking down and overexpression was used to analyze the functions about Chordin-like 2. Enzyme-linked immunosorbent assay (ELISA) was used to detect the secretion of bone morphogenetic proteins 4 (BMP4). Flow cytometry was used to analyze cell cycle. Cell morphology was observed by phase contrast microscope (PCM).ResultsIn normal RPE cells, CHRDL2 was firstly upregulated and followed a downregulation but eventually, it was expressed higher than the cells which undergone epithelial-mesenchymal transition (EMT). After knocking down CHRDL2, the secretion of BMP4 was decreased, RPE-related genes (OTX2, MITF, RPE65) were downregulated while EMT-related genes (SNAI1, VIM) were upregulated. However, the expression of these related genes after overexpression of CHRDL2 had contrary results. Chordin-like 2 also regulated the cell cycle by regulating BMP pathway. When CHRDL2 was knocked down, more fRPE cells stayed in S phase of cell cycle, while adding BMP4 reduced the proportion of the cells in S phase. However, overexpression of CHRDL2 increased more BMP4 secretion, this effect decreased the number of cells in S phase, but exogenous BMP inhibitor also could change this effect. At last, in the process of RPE cells differentiation, adding BMP4 at early stage could intervene normal RPE differentiation. Compared with BMP4, inhibiting BMP pathway had no significant negative effect at early stage, but suppressed differentiation at late stage.ConclusionBMP pathway can be activated in a correct temporal order, otherwise, the cells have incorrect differentiation orientation. And Chordin-like 2 plays a role in dynamic regulation of BMP pathway and it also regulates the differentiation of RPE cells. Therefore, this research enlightens a new direction to inhibit EMT and promote cell redifferentiation after injury.

Dataset Information

Expression of Kielin/chordin-like protein is regulated by BMP-2 in osteoblasts.

Publications

Expression of Kielin/chordin-like protein is regulated by BMP-2 in osteoblasts.

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