Aims: Calcific aortic valve disease (CAVD) affects 2-6% of the population over 65 years, and age, gender, smoking, overweight, dyslipidemia, diabetes contribute to the development of this disease. CAVD results, in part, from the osteoblast differentiation of human valvular interstitial cells (VICs). This study aims to elucidate the effects of leptin on osteoblast phenotype of VICs and the signalling pathways involved.
Methods: Patients who underwent aortic valve replacement for CAVD (n = 43) were included in this study. Patients with coronary artery disease (CAD) without CAVD (n = 129) were used as controls.
Results: Patients with CAVD had higher serum leptin concentrations than CAD patients (p = 0.002). Leptin was found in calcific aortic valves, with higher concentrations in calcified versus non-calcified zones (p = 0.01). Chronic leptin stimulation of human VICs enhanced alkaline phosphatase (ALP) activity and ALP, BMP-2 and RUNX2 expression and decreased osteopontin expression. Moreover, inhibiting Akt or ERK during leptin stimulation lowered the expression of osteoblast markers in VIC.
Conclusions: Taken together, these findings indicate that leptin plays a critical role in CAVD development by promoting osteoblast differentiation of human aortic VICs in an Akt- and ERK-dependent manner. This study highlights the role of leptin in CAVD development, and further studies are needed to determine whether reducing circulating leptin levels or blocking leptin actions on VICs is efficient to slow CAVD progression.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s00592-017-0980-3 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Mechanistic studies of chondroitin sulfate/dermatan sulfate isolated from freshwater fish discards on osteogenesis in MC3T3-E1 cells.
Glycoconj J
January 2025
Department of Molecular Nutrition, CSIR-CFTRI, Mysuru, 570020, India.
Glycosaminoglycans (GAGs) are essential bone extracellular matrix molecules that regulate osteoblast differentiation. Numerous studies have explored endogenous and exogenous GAG osteoanabolic activities using appropriate in vitro and in vivo models. However, GAGs' underlying the mechanism of action and structure-function relationships need to be elucidated in detail.
View Article and Find Full Text PDFA BMP-2 sustained-release scaffold accelerated bone regeneration in rats via the BMP-2 consistent activation maintained by a non-sulfate polysaccharide.
Biomed Mater
January 2025
School of Food Science and Technology, Dalian Polytechnic University, SKL of Marine Food Processing & Safety Control, National Engineering Research Center of Seafood, Dalian 116034, People's Republic of China.
Bone morphogenetic protein 2 (BMP-2) and a polysaccharide (SUP) were embedded in the calcium phosphate cement (CPC) scaffold, and the bone repair ability was evaluated. The new scaffolds were characterized using x-ray diffraction, Fourier transform-infrared, scanning electron microscopy, and energy dispersive spectroscopy analyses. CPC-BMP2-SUPH scaffold promoted the BMP-2 release by 1.
View Article and Find Full Text PDFNuclear factor I-C regulates intramembranous bone formation via control of FGF signalling.
Heliyon
January 2025
Department of Oral Histology-Developmental Biology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Republic of Korea.
Our previous studies indicate that NFI-C is essential for tooth root development and endochondral ossification. However, its exact role in calvarial intramembranous bone formation remains unclear. In this study, we demonstrate that the disruption of the gene leads to defects in intramembranous bone formation, characterized by decreased osteogenic proliferative activity and reduced osteoblast differentiation during postnatal osteogenesis.
View Article and Find Full Text PDF3D-Printed PCL/SrHA@DFO Bone Tissue Engineering Scaffold with Bone Regeneration and Vascularization Function.
ACS Appl Bio Mater
January 2025
School of Materials Science and Physics, School of Chemical Engineering and Technology, China University of Mining and Technology, Xuzhou 221116, Jiangsu, China.
The application of a three-dimensional (3D)-printed biological functional scaffold in the repair of bone defects is a promising strategy. In this study, strontium-containing hydroxyapatite (SrHA) powder was synthesized by the hydrothermal method, and then poly(ε-caprolactone) (PCL)/HA and PCL/SrHA composite scaffolds were prepared by the high-temperature melt extrusion 3D printing technology. The basic physical and chemical properties, in vitro biological properties, osteogenesis, and angiogenesis abilities of the scaffold were studied.
View Article and Find Full Text PDFMARCH5 ameliorates aortic valve calcification via RACGAP1-DRP1 pathway associated mitochondrial quality control.
Biochim Biophys Acta Mol Cell Res
January 2025
Laboratory of Cardiac Structure and Function, Institute of Cardiovascular Diseases, West China Hospital, Sichuan University, Chengdu 610041, PR China; Department of Cardiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Cardiac Structure and Function Research Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, PR China. Electronic address:
Background: Mitochondrial E3 ubiquitin ligase (MARCH5) as an important regulator in maintaining mitochondrial function. Our aims were to investigate the role and mechanism of MARCH5 in aortic valve calcification.
Methods: Human aortic valves, both calcified and non-calcified, were analyzed for MARCH5 expression using western blot.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!