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Rejuvenation of the inflammatory system stimulates fracture repair in aged mice
Author(s) -
Xing Zhiqing,
Lu Chuanyong,
Hu Diane,
Miclau Theodore,
Marcucio Ralph S.
Publication year - 2010
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.21087
Subject(s) - bone healing , bone marrow , juvenile , medicine , transplantation , inflammation , bone marrow stem cell , stem cell , pathology , immunology , biology , surgery , microbiology and biotechnology , genetics
Age significantly reduces the regenerative capacity of the skeleton, but the underlying causes are unknown. Here, we tested whether the functional status of inflammatory cells contributes to delayed healing in aged animals. We created chimeric mice by bone marrow 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. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:1000–1006, 2010