Improved Bone Healing Seen in Mice With Lower Apolipoprotein E Levels

By Will Boggs MD

October 24, 2019

NEW YORK (Reuters Health) - Lower levels of circulating apolipoprotein E (ApoE) are associated with improved bone-fracture healing in mice, researchers report.

"We were most interested in our finding that circulating ApoE plays a key inhibitory role in fracture healing," Dr. Gurpreet S. Baht of Duke University, in Durham, North Carolina, told Reuters Health by email. "This was especially intriguing once we identified circulating ApoE to increase with age in patients and mice."

Non-union or delayed union complicates as many as 10% of fracture cases, and this rate is higher in the elderly population. Although ApoE polymorphisms are associated with decreased bone-mineral density and increased risk of hip and vertebral fracture, the role of ApoE in fracture healing remains unclear.

Dr. Baht's team used their established mouse tibial-fracture model to investigate the role of circulating ApoE in fracture healing. In ApoE-knockout mice, the loss of ApoE was associated with increased bone deposition in the fracture callus without significant changes in other aspects of bone repair.

In a cell culture model of osteoblast differentiation, recombinant ApoE treatment was associated with decreased osteoblast differentiation and activity, which were related to decreases in glycolytic metabolism.

In the fracture model, higher circulating levels of ApoE were associated with diminished fracture healing.

ApoE levels were two-fold higher in patients aged 75-85 years than in patients aged 35-45 years and were three-fold higher in aged mice (24 months old) than in young mice (4 months old), the researchers report in JCI Insight, online September 19.

In aged mice, decreasing levels of circulating ApoE using a small-interfering RNA (siRNA) system was associated with substantial improvements in fracture healing.

"I think this work is exciting in that we have identified a new aging factor that inhibits fracture healing," Dr. Baht said. "This means we have identified a novel therapeutic target for improving bone healing. However, the work is still in its infancy, and more studies need to be conducted to better understand ApoE's role in fracture repair."

"Another novelty within this work is linking osteoblast cellular metabolism to fracture healing," he said. "Understanding the effects of cellular metabolism on osteoblast biology is a developing area of research, and here we add fracture healing and ApoE to this field."


JCI Insight 2019.