Victoria Ryder and Dr. Robert Seegmiller, Zoology
Introduction
Cartilage collagen mutations can alter the load-bearing properties of articular cartilage (AC), possibly leading to premature osteoarthritis. AC consists mainly of types II, VI, IX, X, and XI collagen.1 Collagen fibrils in AC are heteropolymers of types II, IX, and XI collagen2. Type II is the major constituent, making up 95% of the fibril, while types IX and XI are minor components. Collagen fibrillar meshwork is essential as it gives AC its structural and tensile strength. Type XI collagen plays a role in dictating fibril diameter, thus playing a role in the AC’s strength. Mutations in the Col11a1 gene can cause abnormalities in the cartilage.
Chondrodysplasia (cho) is a lethal autosomal recessive condition in mice due to the deletion of one nucleotide in the Col11a1 gene and is associated with Stickler and Marshall syndromes in humans. The cho heterozygote is similar to Stickler and Marshall syndromes in that the phenotype is normal (not dwarfed) but a copy of the mutation is still inherited. Stickler patients demonstrate osteoarthritis as early as 30 years old.3 The focus of this project was to determine if the mutated Col11a1 copy leads to premature osteoarthritis in the cho heterozygote.
Materials and Methods
Control and cho/+ knee joints were fixed, sectioned frontally, and stained with Safranin O-Fast Green at four different ages: 6, 9, 12, and 15 months. Articula r cartilages were then examined for evidence of degenerative changes.
Results
In control mice, cellularity (cells per unit area) decreased from 1.6 at 6 months to 1.4 at 15 months. This difference was not significant. At 6 and 9 months, cells were organized into columns but appeared organized into clusters at 12 and 15 months. Surface erosion and acellular, poorly stained lesions were first observed at 15 months. Relative to control, cellularity in the mutant was the same at 6 months but increased to 1.9 at 9 months, a significant change of 32% (p<.05). Cellularity differences were noted mainly in the superficial region, a significant increase of 46% (p<.05). Cell clustering was observed as early as 9 months and continued to 12 and 15 months in the mutant. Surface erosion and lesions were evident as early as 12 months and continued to 15 months.
Conclusion
Hypercellularity, cell clustering, surface erosion, and acellular lesions are typical indicators of osteoathritis in humans. Therefore, these changes indicate cho heterozygous mice develop osteoarthritis as early as 9 months, much earlier than spontaneous osteoarthritis in control mice.
References
- Buchwalter J, Mankin H (1998) Articular Cartilage: Tissue Design and Chondrocyte-Matrix Interactions. AAOS Instructional Course Lectures 47: 477-86.
- Young RD, Lawrence PA, Duance VC, Aigner T, Monaghan P (2000) Immunolocalization of Collagen Types II and III in Single Fibrils of Human Articular Cartilage. J Histochem Cytochem 48(3):423-32. 3Snead MP, Yates JR (1999) Clinical and Molecular Genetics of Stickler Syndrome J Med Genet 36(5):353- 9.