Skeleton-secreted PDGF-BB mediates arterial stiffening

J Clin Invest. 2021 Oct 15;131(20):e147116. doi: 10.1172/JCI147116.


Evidence links osteoporosis and cardiovascular disease but the cellular and molecular mechanisms are unclear. Here we identify skeleton-secreted platelet-derived growth factor-BB (PDGF-BB) as a key mediator of arterial stiffening in response to aging and metabolic stress. Aged mice and those fed high-fat diet (HFD), relative to young mice and those fed normal chow food diet, respectively, had higher serum PDGF-BB and developed bone loss and arterial stiffening. Bone/bone marrow preosteoclasts in aged mice and HFD mice secrete an excessive amount of PDGF-BB, contributing to the elevated PDGF-BB in blood circulation. Conditioned medium prepared from preosteoclasts stimulated proliferation and migration of the vascular smooth muscle cells. Conditional transgenic mice, in which PDGF-BB is overexpressed in preosteoclasts, had 3-fold higher serum PDGF-BB concentration and developed simultaneous bone loss and arterial stiffening spontaneously at a young age. Conversely, in conditional knockout mice, in which PDGF-BB is deleted selectively in preosteoclasts, HFD did not affect serum PDGF-BB concentration; as a result, HFD-induced bone loss and arterial stiffening were attenuated. These studies confirm that preosteoclasts are a main source of excessive PDGF-BB in blood circulation during aging and metabolic stress and establish the role of skeleton-derived PDGF-BB as an important mediator of vascular stiffening.

Keywords: Bone Biology; Vascular Biology.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging
  • Animals
  • Becaplermin / blood
  • Becaplermin / physiology*
  • Bone Resorption / etiology
  • Diet, High-Fat
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscle, Smooth, Vascular / cytology
  • Myocytes, Smooth Muscle / physiology
  • Osteoclasts / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Vascular Stiffness / physiology*


  • Becaplermin