Lowering circulating apolipoprotein E levels improves aged bone fracture healing.

Published online

Journal Article

Age is a well-established risk factor for impaired bone fracture healing. Here, we identify a role for apolipoprotein E (ApoE) in age-associated impairment of bone fracture healing and osteoblast differentiation, and we investigate the mechanism by which ApoE alters these processes. We identified that, in both humans and mice, circulating ApoE levels increase with age. We assessed bone healing in WT and ApoE-/- mice after performing tibial fracture surgery: bone deposition was higher within fracture calluses from ApoE-/- mice. In vitro recombinant ApoE (rApoE) treatment of differentiating osteoblasts decreased cellular differentiation and matrix mineralization. Moreover, this rApoE treatment decreased osteoblast glycolytic activity while increasing lipid uptake and fatty acid oxidation. Using parabiosis models, we determined that circulating ApoE plays a strong inhibitory role in bone repair. Using an adeno-associated virus-based siRNA system, we decreased circulating ApoE levels in 24-month-old mice and demonstrated that, as a result, fracture calluses from these aged mice displayed enhanced bone deposition and mechanical strength. Our results demonstrate that circulating ApoE as an aging factor inhibits bone fracture healing by altering osteoblast metabolism, thereby identifying ApoE as a new therapeutic target for improving bone repair in the elderly.

Full Text

Duke Authors

Cited Authors

  • Huang, R; Zong, X; Nadesan, P; Huebner, JL; Kraus, VB; White, JP; White, PJ; Baht, GS

Published Date

  • September 19, 2019

Published In

Volume / Issue

  • 4 / 18

PubMed ID

  • 31534056

Pubmed Central ID

  • 31534056

Electronic International Standard Serial Number (EISSN)

  • 2379-3708

Digital Object Identifier (DOI)

  • 10.1172/jci.insight.129144

Language

  • eng

Conference Location

  • United States