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 journalArticle

45 Citations (Scopus)

Abstract

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
Volume28
Issue number8
DOIs
StatePublished - Aug 1 2010
Externally publishedYes

Fingerprint

Rejuvenation
Fracture Healing
Bone Marrow
Bony Callus
Chondrocytes
Osteoblasts
Osteogenesis
Skeleton
Transplantation
Bone and Bones

Keywords

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

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

Cite this

Rejuvenation of the inflammatory system stimulates fracture repair in aged mice. / Xing, Zhiqing; Lu, Chuanyong; Hu, Diane; Miclau, Theodore; Marcucio, Ralph S.

In: Journal of Orthopaedic Research, Vol. 28, No. 8, 01.08.2010, p. 1000-1006.

Research output: Contribution to journalArticle

Xing, Zhiqing ; Lu, Chuanyong ; Hu, Diane ; Miclau, Theodore ; Marcucio, Ralph S. / Rejuvenation of the inflammatory system stimulates fracture repair in aged mice. In: Journal of Orthopaedic Research. 2010 ; Vol. 28, No. 8. pp. 1000-1006.
@article{a3bb33cc0e84496cbae4c49302addc68,
title = "Rejuvenation of the inflammatory system stimulates fracture repair in aged mice",
abstract = "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.",
keywords = "Aging, Bone marrow transplant, Bone repair, Fracture, Inflammation, Rejuvenation",
author = "Zhiqing Xing and Chuanyong Lu and Diane Hu and Theodore Miclau and Marcucio, {Ralph S.}",
year = "2010",
month = "8",
day = "1",
doi = "10.1002/jor.21087",
language = "English (US)",
volume = "28",
pages = "1000--1006",
journal = "Journal of Orthopaedic Research",
issn = "0736-0266",
publisher = "John Wiley and Sons Inc.",
number = "8",

}

TY - JOUR

T1 - Rejuvenation of the inflammatory system stimulates fracture repair in aged mice

AU - Xing, Zhiqing

AU - Lu, Chuanyong

AU - Hu, Diane

AU - Miclau, Theodore

AU - Marcucio, Ralph S.

PY - 2010/8/1

Y1 - 2010/8/1

N2 - 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.

AB - 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.

KW - Aging

KW - Bone marrow transplant

KW - Bone repair

KW - Fracture

KW - Inflammation

KW - Rejuvenation

UR - http://www.scopus.com/inward/record.url?scp=77954717770&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77954717770&partnerID=8YFLogxK

U2 - 10.1002/jor.21087

DO - 10.1002/jor.21087

M3 - Article

C2 - 20108320

AN - SCOPUS:77954717770

VL - 28

SP - 1000

EP - 1006

JO - Journal of Orthopaedic Research

JF - Journal of Orthopaedic Research

SN - 0736-0266

IS - 8

ER -