Skeleton-secreted PDGF-BB mediates arterial stiffening

Area of Science:

• Biomedical Science
• Cardiovascular Biology
• Bone Biology

Background:

• Osteoporosis and cardiovascular disease share links, but underlying mechanisms remain elusive.
• Aging and metabolic stress contribute to both bone loss and arterial stiffening.
• Platelet-derived growth factor-BB (PDGF-BB) is implicated in vascular remodeling.

Purpose of the Study:

• To identify the cellular and molecular mechanisms linking osteoporosis and cardiovascular disease.
• To investigate the role of skeleton-secreted PDGF-BB in arterial stiffening.
• To determine the contribution of preosteoclasts to elevated PDGF-BB levels.

Main Methods:

• Comparative analysis of aged and young mice, and mice on high-fat diet (HFD) versus normal chow.
• Assessment of serum PDGF-BB levels, bone density, and arterial stiffness.
• Utilized conditional transgenic and knockout mouse models with altered PDGF-BB expression in preosteoclasts.

Main Results:

• Aged and HFD mice exhibited higher serum PDGF-BB, bone loss, and arterial stiffening.
• Preosteoclasts in aged/HFD mice secreted excessive PDGF-BB, increasing blood levels.
• Overexpression of PDGF-BB in preosteoclasts led to spontaneous bone loss and arterial stiffening.
• Selective deletion of PDGF-BB in preosteoclasts attenuated HFD-induced bone loss and arterial stiffening.

Conclusions:

• Preosteoclasts are a primary source of excess circulating PDGF-BB during aging and metabolic stress.
• Skeleton-derived PDGF-BB is a critical mediator of vascular stiffening.
• Targeting preosteoclast PDGF-BB secretion may offer therapeutic strategies for related conditions.