The beneficial effects of exercise on cartilage are lost in mice with reduced levels of ECSOD in tissues

Kathryn M. Pate, Vanessa D. Sherk, R. Dana Carpenter, Michael Weaver, Silvia Crapo, Fabienne Gally, Lillian S. Chatham, David A. Goldstrohm, James D. Crapo, Wendy M. Kohrt, Russell P. Bowler, Rebecca E Deegan, Elizabeth A. Regan

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Osteoarthritis (OA) is associated with increased mechanical damage to joint cartilage. We have previously found that extracellular superoxide dismutase (ECSOD) is decreased in OA joint fluid and cartilage, suggesting oxidant damage may play a role in OA. We explored the effect of forced running as a surrogate for mechanical damage in a transgenic mouse with reduced ECSOD tissue binding. Transgenic mice heterozygous (Het) for the human ECSOD R213G polymorphism and 129-SvEv (wild-type, WT) mice were exposed to forced running on a treadmill for 45 min/day, 5 days/wk, over 8 wk. At the end of the running protocol, knee joint tissue was obtained for histology, immunohistochemistry, and protein analysis. Sedentary Het and WT mice were maintained for comparison. Whole tibias were studied for bone morphometry, finite element analysis, and mechanical testing. Forced running improved joint histology in WT mice. However, when ECSOD levels were reduced, this beneficial effect with running was lost. Het ECSOD runner mice had significantly worse histology scores compared with WT runner mice. Runner mice for both strains had increased bone strength in response to the running protocol, while Het mice showed evidence of a less robust bone structure in both runners and untrained mice. Reduced levels of ECSOD in cartilage produced joint damage when joints were stressed by forced running. The bone tissues responded to increased loading with hypertrophy, regardless of mouse strain. We conclude that ECSOD plays an important role in protecting cartilage from damage caused by mechanical loading.

Original languageEnglish (US)
Pages (from-to)760-767
Number of pages8
JournalJournal of Applied Physiology
Volume118
Issue number6
DOIs
StatePublished - Mar 15 2015

Fingerprint

Superoxide Dismutase
Cartilage
Running
Joints
Osteoarthritis
Bone and Bones
Histology
Transgenic Mice
Finite Element Analysis
Knee Joint
Tibia
Oxidants
Hypertrophy
Immunohistochemistry

Keywords

  • Bone
  • Cartilage
  • Extracellular superoxide dismutase
  • Osteoarthritis
  • Running

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Pate, K. M., Sherk, V. D., Carpenter, R. D., Weaver, M., Crapo, S., Gally, F., ... Regan, E. A. (2015). The beneficial effects of exercise on cartilage are lost in mice with reduced levels of ECSOD in tissues. Journal of Applied Physiology, 118(6), 760-767. https://doi.org/10.1152/japplphysiol.00112.2014

The beneficial effects of exercise on cartilage are lost in mice with reduced levels of ECSOD in tissues. / Pate, Kathryn M.; Sherk, Vanessa D.; Carpenter, R. Dana; Weaver, Michael; Crapo, Silvia; Gally, Fabienne; Chatham, Lillian S.; Goldstrohm, David A.; Crapo, James D.; Kohrt, Wendy M.; Bowler, Russell P.; Deegan, Rebecca E; Regan, Elizabeth A.

In: Journal of Applied Physiology, Vol. 118, No. 6, 15.03.2015, p. 760-767.

Research output: Contribution to journalArticle

Pate, KM, Sherk, VD, Carpenter, RD, Weaver, M, Crapo, S, Gally, F, Chatham, LS, Goldstrohm, DA, Crapo, JD, Kohrt, WM, Bowler, RP, Deegan, RE & Regan, EA 2015, 'The beneficial effects of exercise on cartilage are lost in mice with reduced levels of ECSOD in tissues', Journal of Applied Physiology, vol. 118, no. 6, pp. 760-767. https://doi.org/10.1152/japplphysiol.00112.2014
Pate, Kathryn M. ; Sherk, Vanessa D. ; Carpenter, R. Dana ; Weaver, Michael ; Crapo, Silvia ; Gally, Fabienne ; Chatham, Lillian S. ; Goldstrohm, David A. ; Crapo, James D. ; Kohrt, Wendy M. ; Bowler, Russell P. ; Deegan, Rebecca E ; Regan, Elizabeth A. / The beneficial effects of exercise on cartilage are lost in mice with reduced levels of ECSOD in tissues. In: Journal of Applied Physiology. 2015 ; Vol. 118, No. 6. pp. 760-767.
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abstract = "Osteoarthritis (OA) is associated with increased mechanical damage to joint cartilage. We have previously found that extracellular superoxide dismutase (ECSOD) is decreased in OA joint fluid and cartilage, suggesting oxidant damage may play a role in OA. We explored the effect of forced running as a surrogate for mechanical damage in a transgenic mouse with reduced ECSOD tissue binding. Transgenic mice heterozygous (Het) for the human ECSOD R213G polymorphism and 129-SvEv (wild-type, WT) mice were exposed to forced running on a treadmill for 45 min/day, 5 days/wk, over 8 wk. At the end of the running protocol, knee joint tissue was obtained for histology, immunohistochemistry, and protein analysis. Sedentary Het and WT mice were maintained for comparison. Whole tibias were studied for bone morphometry, finite element analysis, and mechanical testing. Forced running improved joint histology in WT mice. However, when ECSOD levels were reduced, this beneficial effect with running was lost. Het ECSOD runner mice had significantly worse histology scores compared with WT runner mice. Runner mice for both strains had increased bone strength in response to the running protocol, while Het mice showed evidence of a less robust bone structure in both runners and untrained mice. Reduced levels of ECSOD in cartilage produced joint damage when joints were stressed by forced running. The bone tissues responded to increased loading with hypertrophy, regardless of mouse strain. We conclude that ECSOD plays an important role in protecting cartilage from damage caused by mechanical loading.",
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