Rejuvenation of the inflammatory system stimulates fracture repair in aged mice

Zhiqing Xing, Chuanyong Lu, Diane Hu, Theodore Miclau, Ralph S. Marcucio

Research output: Contribution to journalArticlepeer-review

71 Scopus citations


Age significantly reduces the regenerative capacity of the skeleton, but the underlying causes are unknown. Here, we tested whether the functional status ofinflammatory cells contributes to delayed healing in aged animals.Wecreated chimeric mice by bonemarrow transplantation after lethal irradiation. In this model, chondrocytes and osteoblasts in the regenerate are derived exclusively from host cells while inflammatory cells are derived from the donor. Using this model, the inflammatory system of middle-aged mice (12 month old) was replaced by transplanted bone marrow from juvenile mice (4 weeks old), or age-matched controls. We found that the middle-aged mice receiving juvenile bone marrow had larger calluses and more bone formation during early stages and faster callus remodeling at late stages of fracture healing, indicating that inflammatory cells derived from the juvenile bone marrow accelerated bone repair in the middle-aged animals. In contrast, transplanting bone marrow from middle-aged mice to juvenile mice did not alter the process of fracture healing in juvenile mice. Thus, the roles of inflammatory cells in fracture healing may be age-related, suggesting the possibility of enhancing fracture healing in aged animals by manipulating the inflammatory system.

Original languageEnglish (US)
Pages (from-to)1000-1006
Number of pages7
JournalJournal of Orthopaedic Research
Issue number8
StatePublished - Aug 2010
Externally publishedYes


  • Aging
  • Bone marrow transplant
  • Bone repair
  • Fracture
  • Inflammation
  • Rejuvenation

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine


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