FGF18 inhibits MC3T3-E1 cell osteogenic differentiation via the ERK signaling pathway

Zhai, Feng; Song, Na; Ma, Jian; Gong, Weiyue; Tian, Haishan; Li, Xiaokun; Jiang, Chao; Wang, Haijun

doi:10.3892/mmr.2017.7088

Cited by 14 publications

(9 citation statements)

References 34 publications

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“…Although MAPK are mostly considered as having a pro‐anabolic role in osteoblast and bone development, a few number of studies demonstrated that increased MAPK phosphorylation could also be associated with decreased osteoblast differentiation or bone mineralization . It suggests that the overall role of MAPK in osteoblasts may vary substantially based on the stage of osteoblast differentiation and the anatomic location considered.…”

Section: Discussionmentioning

confidence: 99%

Homozygous Loss-of-Function Mutations in CCDC134 Are Responsible for a Severe Form of Osteogenesis Imperfecta

Brunelle

Baujat

Huber

et al. 2020

Journal of Bone and Mineral Research

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Osteogenesis imperfecta (OI) is a primary bone fragility disorder with an estimated prevalence of 1 in 15,000 births. The majority of OI cases are inherited in an autosomal-dominant manner, while 5% to 10% have recessive or X-linked inheritance. Up to now, approximately 5% of OI cases remain without mutation demonstrated, supporting the involvement of other genes in the disease spectrum. By whole-exome sequencing, we identified a homozygous variant (c.2T>C) in CCDC134 gene in three patients from two unrelated families with severe bone fragility that did not respond to bisphosphonate treatment, short stature, and gracile long bones with pseudarthroses but no dentinogenesis imperfecta. CCDC134 encodes a secreted protein widely expressed and implicated in the regulation of some mitogen-activated protein kinases (MAPK) signaling pathway. Western blot and immunofluorescence analyses confirmed the absence of CCDC134 protein in patient cells compared with controls. Furthermore, we demonstrated that CCDC134 mutations are associated with increased Erk1/2 phosphorylation, decreased OPN mRNA and COL1A1 expression and reduced mineralization in patient osteoblasts compared with controls. These data support that CCDC134 is a new gene involved in severe progressive deforming recessive osteogenesis imperfecta (type III).

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Section: Discussionmentioning

confidence: 99%

Homozygous Loss-of-Function Mutations in CCDC134 Are Responsible for a Severe Form of Osteogenesis Imperfecta

Brunelle

Baujat

Huber

et al. 2020

Journal of Bone and Mineral Research

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“…The present study focused on the effects of miR-135b-5p on osteogenic differentiation and osteoblast proliferation. Therefore, the mouse pre-osteoblast cell line MC3T3-E1, which is widely used in osteogenic differentiation investigation (30)(31)(32), was selected for this study. Osteogenic differentiation was induced in MC3T3-E1 cells.…”

Section: Discussionmentioning

confidence: 99%

Abnormal expression of miR‑135b‑5p in bone tissue of patients with osteoporosis and its role and mechanism in osteoporosis progression

et al. 2019

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Osteoporosis (OP) is an age-related bone disease occurring worldwide. Osteoporotic fracture is one of the leading causes of disability and death in elderly patients. MicroRNAs (miRNAs/miRs) are key molecular regulatory factors in bone remodeling processes. The present study investigated the expression and mechanism of miR-135b-5p in patients with osteoporosis. The present results suggested that miR-135b-5p was upregulated in bone tissue fragments of patients with osteoporosis compared with the control patients. MC3T3-E1 cells were used to perform osteogenic differentiation induction. Reverse transcription-quantitative PCR and western blot assay were used to detect the mRNA and protein expression levels of the osteogenic markers osteocalcin (OC), Osterix and alkaline phosphatase (ALP). A specific kit was used for detecting ALP activity. The present results indicated that the mRNA expression levels of OC, Osterix and ALP significantly increased on the 7 and 14th day after osteogenic differentiation induction compared with the control group. Protein expression levels of OC, Osterix and ALP also increased on the 7 and 14th day after induction. ALP assay showed that ALP activity was significantly increased on the 7 and 14th day after induction. In addition, the present study found that miR-135b-5p was downregulated in MC3T3-E1 cells 7 and 14 days after osteogenic differentiation induction. The results of TargetScan analysis and dual luciferase reporter gene assay indicated that runt-related transcription factor 2 (RUNX2) was a direct target gene of miR-135b-5p. RUNX2 was upregulated in MC3T3-E1 cells on the 7 and 14th day after induction. Moreover, the present study found that compared with the osteogenic differentiation induction group, miR-135b-5p mimic significantly decreased OC, Osterix and ALP expression, and reduced ALP activity in MC3T3-E1 cells. However, these reductions were reversed following overexpression of RUNX2. The present results showed that miR-135b-5p mimic significantly reduced cell viability in MC3T3-E1 cells and induced cell apoptosis, and these effects were significantly reversed following RUNX2 overexpression. In summary, the present results suggested that miR-135-5p participated in the occurrence and development of osteoporosis via inhibition of osteogenic differentiation and osteoblast growth by targeting RUNX2. The present study suggested a novel potential target that may faciliate the treatment of osteoporosis, and further study is required to examine this possibility.

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“…Total proteins were extracted from CRC cells. The cells were lysed in cold lysis buffer (60 mM Tris-HCl at pH 7.4, 150 mM NaCl, 0.25% SDS and 1% Tergitol-type NP-40) containing 10 mM NaF, 1 mM Na 3 VO 4 and complete protease inhibitor (Roche Diagnostics, Basel, Switzerland) for 30 min on ice, and were then centrifuged at 10,000 × g at 4°C for 15 min as previously described ( 25 ). A bicinchoninic acid protein assay was used to determine protein concentration.…”

Section: Methodsmentioning

confidence: 99%

COL1A1: A potential therapeutic target for colorectal cancer expressing wild-type or mutant KRAS

et al. 2018

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Colorectal cancer (CRC) treatment primarily relies on chemotherapy along with surgery, radiotherapy and, more recently, targeted therapy at the late stages. However, chemotherapeutic drugs have high cytotoxicity, and the similarity between the effects of these drugs on cancerous and healthy cells limits their wider use in clinical settings. Targeted monoclonal antibody treatment may compensate for this deficiency. Epidermal growth factor receptor (EGFR)-targeted drugs have a positive effect on CRC with intact KRAS proto-oncogene GTPase (KRAS or KRASWT), but may be ineffective or harmful in patients with KRAS mutations (KRASMUT). Therefore, it is important to identify drug target genes that are uniformly effective with regards to KRASWT and KRASMUT CRC. The present study performed gene expression analysis, and identified 294 genes upregulated in KRASWT and KRASMUT CRC samples. Collagen type I α 1 (COL1A1) was identified as the hub gene through STRING and Cytoscape analyses. Consistent with results obtained from Oncomine, a cancer microarray database and web-based data-mining platform, it was demonstrated that the expression of COL1A1 was significantly upregulated in CRC tissues and cell lines regardless of KRAS status. Inhibition of COL1A1 in KRASWT and KRASMUT CRC cell lines significantly decreased cell proliferation and invasion. In addition, increased COL1A1 expression in CRC was significantly associated with serosal invasion, lymph metastases and hematogenous metastases. Taken together, the findings of the present study indicated that COL1A1 may serve as a candidate diagnostic biomarker and a promising therapeutic target for CRC.

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FGF18 inhibits MC3T3-E1 cell osteogenic differentiation via the ERK signaling pathway

Cited by 14 publications

References 34 publications

Homozygous Loss-of-Function Mutations in CCDC134 Are Responsible for a Severe Form of Osteogenesis Imperfecta

Homozygous Loss-of-Function Mutations in CCDC134 Are Responsible for a Severe Form of Osteogenesis Imperfecta

Abnormal expression of miR‑135b‑5p in bone tissue of patients with osteoporosis and its role and mechanism in osteoporosis progression

COL1A1: A potential therapeutic target for colorectal cancer expressing wild-type or mutant KRAS

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