GDF10 is a negative regulator of vascular calcification

Area of Science:

• Cardiovascular Biology
• Mineral Metabolism
• Vascular Biology

Background:

• Vascular calcification (VC) is a hallmark of cardiovascular disease in chronic kidney disease (CKD) patients.
• VC involves osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs), a process similar to bone formation.
• Previous work showed loss of T-cell death-associated gene 51 (TDAG51) attenuates VC.

Purpose of the Study:

• To investigate the role of growth differentiation factor 10 (GDF10) in the osteogenic transdifferentiation of VSMCs.
• To determine if GDF10 can be a therapeutic target for vascular calcification.

Main Methods:

• Primary mouse and human VSMCs and ex vivo aortic ring cultures were used.
• Recombinant human GDF10 (rhGDF10) treatment and GDF10 knockout mouse models were employed.
• In vivo studies and analysis of circulating GDF10 in CKD patients with severe VC were performed.

Main Results:

• rhGDF10 treatment mitigated phosphate-induced hydroxyapatite (HA) deposition in VSMCs and aortic rings.
• GDF10 knockout mice exhibited increased HA deposition.
• rhGDF10 reduced runt-related transcription factor 2 expression, a key driver of VSMC osteogenic transdifferentiation.
• In vivo rhGDF10 administration attenuated vitamin D3-induced VC.
• Circulating GDF10 levels were elevated in CKD patients with severe VC.

Conclusions:

• GDF10 acts as an inhibitor of vascular calcification by suppressing VSMC osteogenic transdifferentiation.
• GDF10 represents a potential novel biomarker for severe VC in CKD patients.
• GDF10 may serve as a therapeutic target for managing vascular calcification.