Effects of cigarette smoking on early medial collateral ligament healing in a mouse model

Corey S. Gill, Linda J. Sandell, Hossam B. El-Zawawy, Rick W. Wright

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Cigarette smoking delays the healing process and increases morbidity associated with many common musculoskeletal disorders such as medial collateral ligament (MCL) injury. In the current study, a murine model of MCL healing was used to test the hypothesis that smoking impairs extracellular matrix synthesis after injury. Mice were divided into two groups, a nonsmoking control group and a group exposed to smoke for 2 months prior to surgical MCL injury. Mice were euthanized at 3 and 7 days after surgery. Subsequently, propidium iodine staining was used to quantify cellular density of injured and sham ligaments. Immunohistochemical staining and in situ hybridization to mRNA were used to detect proliferation, apoptosis, and type I collagen gene expression at the site of injury. Cell density increased significantly from baseline to 7 days after injury in control mice. In mice exposed to cigarette smoke, there was a significantly lower cellular density compared to controls at this time point (p = 0.01). There was no difference in proliferation between groups at the site of injury, and the low level of proliferation observed was not sufficient to account for the large increase in cell density by day 7. No evidence of apoptosis was observed in any of the groups at the site of injury. Type I collagen gene expression was higher in controls compared to smokers at day 7. Almost all of the cells in the substance of the injured MCL at day 7 were spindle-shaped and expressed type I collagen, suggesting that increased cell density from day 3 to day 7 represented an increase in ligament cells rather than an increased inflammatory response. We conclude that the decreased cellular density and type I collagen expression in the injured ligament of mice exposed to smoke begin to provide a cellular and molecular basis for delayed or deficient early healing in these animals.

Original languageEnglish (US)
Pages (from-to)2141-2149
Number of pages9
JournalJournal of Orthopaedic Research
Issue number12
StatePublished - Dec 2006
Externally publishedYes


  • Cellular density
  • Ligament
  • MCL
  • Mice
  • Smoking

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine


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