Young Blood Cells Supply Proteins That Speed Fracture Repair

0
Subcapital fracture in a 92-year-old woman. The slow healing of bone fractures, a major issue in aging, may be addressed by therapeutic approaches that exploit factors secreted by youthful macrophages. [Sjoehest, Wikipedia]

Broken bones heal more quickly in the young, presumably because a youthful circulation invigorates the bone repair process. A youthful circulation has even been shown to rejuvenate fracture repair in the old. This we know from experiments in which paired mice, young and old, were surgically connected, as well as studies of old mice that received bone marrow transplants from young mice. What we haven’t known, however, is exactly how youthful blood promotes healing. What factors are present in youthful blood that prove so rejuvenating?

An answer to this question has been proposed by scientists based at Duke University Medical Center. These scientists, led by Benjamin Alman, M.D., chair of the department of orthopedic surgery at Duke, looked for “youth factors” in bone marrow stem cells. The search led the scientists to youthful macrophages, which secrete repair-promoting factors. One especially interesting factor identified by the scientists is low-density lipoprotein receptor-related protein 1 (Lrp1).

Details of the study appeared December 5 in the journal Nature Communications, in an article titled, “Macrophage cells secrete factors including LRP1 that orchestrate the rejuvenation of bone repair in mice.” The article describes how the Duke team used proteomic analysis to distinguish young and old secretomes. That is, the scientists looked at how the proteins secreted by young macrophages differed from those secreted by old macrophages.

“Lrp1 is produced by young cells, and depleting Lrp1 abrogates the ability to rejuvenate fracture repair, while treating old mice with recombinant Lrp1 improves fracture healing,” the article’s authors indicated. “Macrophages and proteins they secrete orchestrate the fracture repair process, and young cells produce proteins that rejuvenate fracture repair in mice.”

Finding ways to speed bone repair is a public health priority that could save both lives and health care expense. The Centers for Disease Control and Prevention reports that more than 800,000 patients a year are hospitalized because of fall injuries, including broken hips, and these hospitalizations cost an average of $30,000.

“Delayed fracture healing is a major health issue in aging,” emphasized Dr. Alman. “And strategies to improve the pace of repair and prevent the need for additional surgeries to achieve healing substantially improve patient outcomes.”

After tissue injury, the body dispatches macrophages to areas of trauma, where they undergo functional changes to coordinate tissue repair. During fracture healing, macrophages are found at the fracture site. But when they’re depleted, fractures will not heal effectively. Macrophage populations and characteristics can change with aging.

“We show that young macrophage cells produce factors that lead to bone formation, and when introduced in older mice, improves fracture healing,” said Gurpreet Baht, Ph.D., assistant professor in orthopedic surgery and a lead author of the study.

“While macrophages are known to play a role in repair and regeneration, prior studies do not identify secreted factors responsible for the effect,” Dr. Alman added. “Here we show that young macrophage cells play a role in the rejuvenation process, and injection of one of the factors produced by the young cells into a fracture in old mice rejuvenates the pace of repair. This suggests a new therapeutic approach to fracture rejuvenation.”

This site uses Akismet to reduce spam. Learn how your comment data is processed.