Naturally occurring osteoarthritis in male mice with an extended lifespan

Dave Ewart, Lindsey Harper, Amy Gravely, Richard A. Miller, Cathy S. Carlson, Richard F. Loeser

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Aim: The purpose of this study was to evaluate whether pharmacologic treatments or genotypes shown to prolong murine lifespan ameliorate the severity of age-associated osteoarthritis. Materials and Methods: Male UM-HET3 mice were fed diets containing 17-α-estradiol, acarbose, nordihydroguaiaretic acid, or control diet per the National Institute on Aging Interventions Testing Program (ITP) protocol. Findings were compared to genetically long-lived male Ames dwarf mice. Stifles were analyzed histologically with articular cartilage structure (ACS) and safranin O scoring as well as with quantitative histomorphometry. Results: Depending on the experimental group, ITP mice were between 450 and 1150 days old at the time of necropsy and 12–15 animals were studied per group. Two age groups (450 and 750 days) with 16–20 animals per group were used for Ames dwarf studies. No differences were found in the ACS or safranin O scores between treatment and control groups in the ITP study. There was high variability in most of the histologic outcome measures. For example, the older UM-HET3 controls had ACS scores of 6.1 ± 5.8 (mean±SD) and Saf O scores of 6.8 ± 5.6. Nevertheless, 17-α-estradiol mice had larger areas and widths of subchondral bone compared to controls, and dwarf mice had less subchondral bone area and width and less articular cartilage necrosis than non-dwarf controls. Conclusions: UM-HET3 mice developed age-related OA but with a high degree of variability and without a significant effect of the tested ITP treatments. High variability was also seen in the Ames dwarf mice but differences in several measures suggested some protection from OA.

Original languageEnglish (US)
Pages (from-to)95-103
Number of pages9
JournalConnective Tissue Research
Volume61
Issue number1
DOIs
StatePublished - Jan 2 2020
Externally publishedYes

Fingerprint

Osteoarthritis
Cartilage
Articular Cartilage
Testing
Nutrition
Estradiol
Bone
Animals
Masoprocol
Acarbose
National Institute on Aging (U.S.)
Stifle
Diet
Bone and Bones
Aging of materials
Necrosis
Therapeutics
Age Groups
Genotype
Outcome Assessment (Health Care)

Keywords

  • Osteoarthritis
  • aging
  • cartilage
  • healthspan
  • lifespan

PubMed: MeSH publication types

  • Journal Article

Cite this

Naturally occurring osteoarthritis in male mice with an extended lifespan. / Ewart, Dave; Harper, Lindsey; Gravely, Amy; Miller, Richard A.; Carlson, Cathy S.; Loeser, Richard F.

In: Connective Tissue Research, Vol. 61, No. 1, 02.01.2020, p. 95-103.

Research output: Contribution to journalArticle

Ewart, Dave ; Harper, Lindsey ; Gravely, Amy ; Miller, Richard A. ; Carlson, Cathy S. ; Loeser, Richard F. / Naturally occurring osteoarthritis in male mice with an extended lifespan. In: Connective Tissue Research. 2020 ; Vol. 61, No. 1. pp. 95-103.
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