The role of PDGF-BB in the bone-vascular relationship during aging
Mone Zaidi1,2,3, Daria Lizneva1,2,3, Tony Yuen1,2,3
1Department of Medicine.
Insights
Bone-derived platelet-derived growth factor-BB (PDGF-BB) links aging and high-fat diets to arterial stiffening. This factor worsens cardiovascular disease and osteoporosis by inhibiting bone formation and increasing vascular stiffness.
Area of Science:
- Biomedical Research
- Cardiovascular Science
- Bone Biology
Background:
- Cardiovascular disease (CVD) and osteoporosis frequently coexist, indicating a potential link between bone health and vascular integrity.
- The bone-vessel connection is further highlighted by associations between bone loss, atherosclerosis, and aortic calcification, particularly in chronic kidney disease patients.
Purpose of the Study:
- To investigate the role of platelet-derived growth factor-BB (PDGF-BB), an angiogenesis factor, in mediating vascular stiffening.
- To explore the contribution of bone-derived PDGF-BB to age-related and diet-induced arterial stiffening.
Main Methods:
- Comparative analysis of serum bone-derived PDGF-BB levels in young versus aged mice and in mice on high-fat diet versus normal chow.
- Utilized genetic models to elucidate the mechanisms by which PDGF-BB influences vascular and bone health.
- Assessed the impact of preosteoclast-derived PDGF-BB on osteoblastic bone formation and vascular stiffness.
Main Results:
- Serum levels of bone-derived PDGF-BB varied significantly with age and diet.
- Bone-derived PDGF-BB was identified as a key mediator of arterial stiffening associated with aging and metabolic stress.
- Increased PDGF-BB production by preosteoclasts during aging led to reduced bone formation and accelerated vascular stiffness.
Conclusions:
- Bone-derived PDGF-BB plays a critical role in the arterial stiffening observed in aging and metabolic disease.
- Targeting circulating PDGF-BB levels presents a potential therapeutic strategy for managing comorbid CVD and osteoporosis.
- These findings offer insights into interconnected age-related diseases, suggesting a common pathway involving PDGF-BB.
Abstract:
Cardiovascular disease (CVD) and osteoporosis often occur together, suggesting an association between CVD and bone loss. Similarly, the correlation of bone loss, atherosclerosis, and aortic calcification, especially in patients with chronic kidney disease, exemplifies a bone-vessel connection. In this issue of the JCI, Santhanam et al. investigated the role of the angiogenesis factor platelet-derived growth factor-BB (PDGF-BB) in vascular stiffening. Serum levels of bone-derived PDGF-BB differed between young and aged mice, and in mice fed a high-fat diet (HFD) compared with those fed normal chow. Experiments with genetic models led the authors to conclude that bone-derived PDGF-BB mediates the hallmark arterial stiffening of aging and metabolic stress. Notably, excessive preosteoclast-derived PDGF-BB production during aging inhibited osteoblastic bone formation and increased circulating PDGF-BB, which in turn, accelerated vascular stiffness. These findings suggest that modifying circulating PDGF-BB levels may benefit patients with CVD, osteoporosis, and other age-related diseases.
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