Premature osteoarthritis in the Disproportionate micromelia (Dmm) mouse.
OBJECTIVE
Degeneration of articular cartilage leads to the development of osteoarthritis (OA), but the molecular pathology of the disease is poorly understood. The Disproportionate micromelia (Dmm) mouse has a deletion mutation in the C-propeptide encoding region of Col2a1, which leads to a defective cartilage matrix. The objective of this study was to determine whether heterozygous (Dmm/+) mice develop premature OA, and could therefore serve as an animal model for studying the molecular pathways leading to OA.


METHODS
Histological analysis was utilized to determine the state of articular cartilage degeneration in Dmm/+ mice at 3, 6, 9, 12, 15, and 22 months of age. Severity of OA was quantified with a modified Mankin scoring system. In addition, articular cartilage thickness, cell density, and the extracellular matrix (ECM) fraction of articular cartilage were quantified.


RESULTS
Articular cartilage erosion was significantly more severe in Dmm/+ than in wild-type (+/+) mice beginning at 9 months, and modified Mankin scoring revealed Dmm/+ articular cartilage to be in a more severe osteoarthritic state as early as 3 months. In addition, Dmm/+ articular cartilage was thinner than +/+ cartilage and showed increased cell density and decreased matrix fraction compared with +/+ from the earliest time points measured.


CONCLUSIONS
The present study demonstrates that Dmm/+ mice develop premature OA. The observed degenerative changes of Dmm/+ articular cartilage closely resemble those of human OA patients, with or without Col2a1 mutations, suggesting that Dmm/+ mice are a useful model for investigating mechanisms involved in OA.
Bomsta
B D
BD
Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602, USA.
Bridgewater
L C
LC
Seegmiller
R E
RE
D000375:Aging / Q000502:physiology; D000818:Animals; D002358:Cartilage, Articular / Q000473:pathology; D002452:Cell Count; D019902:Chondrocytes / Q000473:pathology; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000473:pathology; D006579:Heterozygote; D006614:Hindlimb; D051379:Mice; D008817:Mice, Mutant Strains; D010003:Osteoarthritis / Q000235:genetics* / Q000473:pathology; D011509:Proteoglycans / Q000032:analysis; D012720:Severity of Illness Index
D011509:Proteoglycans