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更新于：2024-11-01

GDF5

更新于：2024-11-01

基本信息

别名

BMP-14、BMP14、Bone morphogenetic protein 14

+ [12]

简介

Growth factor involved in bone and cartilage formation. During cartilage development regulates differentiation of chondrogenic tissue through two pathways. Firstly, positively regulates differentiation of chondrogenic tissue through its binding of high affinity with BMPR1B and of less affinity with BMPR1A, leading to induction of SMAD1-SMAD5-SMAD8 complex phosphorylation and then SMAD protein signaling transduction (PubMed:24098149, PubMed:21976273, PubMed:15530414, PubMed:25092592). Secondly, negatively regulates chondrogenic differentiation through its interaction with NOG (PubMed:21976273). Required to prevent excessive muscle loss upon denervation. This function requires SMAD4 and is mediated by phosphorylated SMAD1/5/8 (By similarity). Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:11276205).

关联

项与 GDF5 相关的药物

M-1673

靶点

GDF5

作用机制

GDF5调节剂

在研机构

Merck KGaA

原研机构

Merck KGaA

在研适应症

骨关节炎

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

MD-05

靶点

GDF5

作用机制

GDF5调节剂

在研机构-

原研机构

BioNet Pharma GmbH

在研适应症-

非在研适应症

牙周疾病

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

MD-08

靶点

GDF5

作用机制

GDF5调节剂

在研机构-

原研机构

BioNet Pharma GmbH

在研适应症-

非在研适应症

牙周疾病

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

项与 GDF5 相关的临床试验

EUCTR2005-003391-37-DE

/ Not yet recruitingN/A

Pilot Study on Safety and explorative Efficacy of MD05 in Comparison with the Medical Device Beta-TCP Mixed with Autogenous Bone Material in Patients Undergoing Two-Stage Unilateral Maxillary Sinus Floor Augmentation - Sinus Lift Study

开始日期2005-12-05

申办/合作机构

BioNet Pharma GmbH

NCT00520377

/ Unknown status临床2期

Pilot Study on Safety and Efficacy of MD05 in Comparison With Beta-TCP in Patients Undergoing Sinus Floor Augmentation

The primary objective is the area of newly formed bone (%) as assessed by histomorphometry with either MD05 or beta-TCP.

开始日期2005-01-01

申办/合作机构

BioNet Pharma GmbH

[+1]

100 项与 GDF5 相关的临床结果

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100 项与 GDF5 相关的转化医学

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0 项与 GDF5 相关的专利（医药）

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878

项与 GDF5 相关的文献（医药）

2024-12-01·Molecular Biology Reports

Intervertebral disc degenerative disease in South Africa: a case-control analysis of selected gene variants

Article

作者: Liebenberg, Adriaan W ; Less, Stephanie ; Benjeddou, Mongi ; Pearce, Keenau

AbstractBackgroundIntervertebral disc (IVD) degenerative disease is a multifactorial disease for which genetics plays an integral role. Several genes, and their variants, associated with the development and progression of IVD degenerative disease have been identified. While several studies have investigated these genes in Asian and European populations, no available evidence exists for the South African population. Therefore, this study aimed to investigate these parameters.Methods and resultsBiological samples were collected in the form of buccal swabs from patients and DNA was extracted using a standard salt-lysis protocol. DNA purity and quantity was assessed by spectrophotometry, and subsequent genotyping was performed using the MassARRAY®System IPLEX extension reaction. For associations between variants and the presence of IVD degenerative disease, odds ratios (OR), confidence intervals (CI), chi-squared analysis and logistic regression was calculated. Age and sex were adjusted for, and Bonferroni’s correction was applied. This study found statistically significant associations for five of the evaluated single nucleotide polymorphisms (SNPs) with IVD degenerative disease, whereby IL-1α rs1304037 and rs1800587, ADAMTs-5 rs162509, and MMP-3 rs632478 demonstrated increased odds of a positive diagnosis for IVD degenerative disease, while decreased odds of IVD degenerative disease were seen for GDF-5 rs143383.ConclusionTo the best of our knowledge, this study represents the first of its kind to investigate the association of gene variants associated with IVD degenerative disease within the South African population. This study has shown that 5 of these gene variants were significantly associated with the presence of IVD degenerative disease, reflecting their integral roles in development and possible progression of the disease.

2024-10-01·Molecular Genetics & Genomic Medicine

Acromesomelic Dysplasia With Homozygosity for a Likely Pathogenic BMPR1B Variant: Postaxial Polydactyly as a Novel Clinical Finding

Article

作者: Knaus, Alexej ; Abdelrazek, Ibrahim M. ; Krawitz, Peter M. ; Abdalla, Ebtesam M. ; Kumar, Sheetal ; Horn, Denise ; Javanmardi, Behnam

ABSTRACTBackgroundAcromesomelic chondrodysplasias are a rare subgroup of the clinically and genetically heterogeneous osteochondrodysplasias that are characterised by abnormalities in the limb development and short stature. Here, we report a 2‐year‐old boy, offspring of consanguineous parents, with acromesomelic dysplasia and postaxial polydactyly in which exome sequencing identified a novel homozygous missense variant in BMPR1B. The patient showed skeletal malformation of both hands and feet that included complex brachydactyly with the thumbs most severely affected, postaxial polydactyly of both hands, shortened toes as well as a bilateral hypoplasia of the fibula.MethodsWhole trio exome sequencing was conducted to identify potential genetic variants in the patient.ResultsThe analysis identified the biallelic variant NM_001203.3:c.821A > G;p.(Gln274Arg) in BMPR1B, a gene encoding bone morphogenetic protein receptor 1B.ConclusionThe skeletal phenotype can be brought in line with the phenotypes of previously reported cases of BMPR1B‐associated chondrodysplasias. However, the postaxial polydactyly described here is a novel clinical finding in a BMPR1B‐related case; notably, it has previously been reported in other acromesomelic dysplasia cases caused by homozygous pathogenic variants in GDF5—a gene which encodes for growth differentiation factor 5, a high‐affinity ligand to BMPR1B.

2024-10-01·Journal of Ethnopharmacology

Transcriptomic analysis reveals the critical role of chemokine signaling in the anti-atherosclerosis effect of Xuefu Zhuyu decoction

Article

作者: Lou, Lixia ; Jia, Dongdong ; Zhang, Dongmei ; Wei, Qiong ; Zhang, Xinyue ; Zhao, Mengzhu ; Chen, Meng ; Cheng, Xu ; Jin, Qiushuo ; Zhao, Yizhou

ETHNOPHARMACOLOGICAL RELEVANCEThe process of atherosclerosis (AS) is complicated. Transcriptomics technology can assist in discovering the underlying mechanisms and exploring the key targets of Traditional Chinese Medicine (TCM) against atherosclerosis.AIMThis study aimed to investigate targets and signaling pathways significantly related to AS and the potential intervention targets of Xuefu Zhuyu decoction by transcriptomics.MATERIALS AND METHODSAS models were established by subjecting ApoE^-/-mice to an 8-week high-fat diet. Structural changes and plaque formation in the aortic root were observed using hematoxylin-eosin staining (HE staining), while Oil Red O staining was employed to visualize lipid deposition within the aortic root plaque. Movat staining and immunohistochemical staining were conducted to examine the components present in the aortic root plaque. Macrophage content within the plaque was observed through immunofluorescence. Additionally, mRNA sequencing was performed on aortic tissues to identify differentially expressed genes. Enrichment analysis was performed using GO and KEGG analysis. Visualization of the protein-protein interaction (PPI) network was achieved using Cytoscape 3.7.1 and STRING. Western blotting (WB) was employed to assess the protein expression of major differentially expressed genes in the aortic tissue. The drug freeze-dried powder of Xuefu Zhuyu decoction was prepared and the RAW264.7 cells were induced by lipopolysaccharide (LPS) to build an in vitro model. Real-time quantitative PCR was employed to measure the mRNA expression of major differential genes.RESULTSAfter ApoE^-/- mice were fed with an 8-week high-fat diet, observable changes included the thinning of the aortic root wall, the accumulation of foam cells within the plaque, and the formation of cholesterol crystals in the model group. Treatment with Xuefu Zhuyu (XFZY) decoction for 12 weeks significantly reduced the lipid deposition and the number of macrophages (P < 0.05) and significantly increased the collagen content within the plaque (P < 0.01). Enrichment analysis revealed a high enrichment of the Cytokine-cytokine receptor interaction pathway and Chemokine signaling pathway. Noteworthy genes involved in this response included Ccl12, Ccl22, Cx3cr1, Ccr7, Ccr2, Tnfrsf25, and Gdf5. Xuefu Zhuyu decoction significantly downregulated the expression of CX3CL1 and CX3CR1 (P < 0.05) and upregulated the expression of GDF5 (P < 0.01). Compared with control group, in cell models, the mRNA expressions of Ccl12, Ccl22, and Ccr2 were significantly upregulated (P < 0.05 or P < 0.01). Xuefu Zhuyu decoction significantly downregulated the expression of Ccl12, Ccl22, Cx3cr1, Ccr7 and Ccr2 (P < 0.05 or P < 0.01).CONCLUSIONXuefu Zhuyu decoction demonstrates effective regulation of plaque components, retarding plaque progression and preserving plaque stability by modulating lipid metabolism and inflammatory responses. Subsequent transcriptome analysis identified the Cytokine-cytokine receptor interaction and Chemokine signaling pathway as potential key pathways for the therapeutic effects of Xuefu Zhuyu decoction. This insight not only provides crucial avenues for further exploration into the mechanisms underlying Xuefu Zhuyu decoction but also offers valuable perspectives and hypotheses for enhancing disease prevention and treatment strategies.

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