Aim: To investigate the molecular features of progressive severities of cartilage damage, within the phenotype of Anteromedial Osteoarthritis of the Knee (AMOA).

Methods: Ten medial tibial plateau specimens were collected from patients undergoing unicompartmental knee replacements.

The cartilage within the area of macroscopic damage was divided into equal thirds: T1(most damaged), to T3 (least damaged). The area of macroscopically undamaged cartilage was taken as a 4th sample, N. The specimens were prepared for histological (Safranin-O and H& E staining) and immunohistochemical analysis (Type I and II Collagen, proliferation and apoptosis).

Immunoassays were undertaken for Collagens I and II and GAG content. Real time PCR compared gene expression between areas T and N.

Results: There was a decrease in OARSI grade across the four areas, with progressively less fibrillation between areas T1, T2 and T3. Area N had an OARSI grade of 0 (normal).

The GAG immunoassay showed decreased levels with increasing severity of cartilage damage (ANOVA P< 0.0001).

There was no significant difference in the Collagen II content or gene expression between areas.

The Collagen I immunohistochemistry showed increased staining within chondrocyte pericellular areas in the undamaged region (N) and immunoassays showed that the Collagen I content of this macroscopically and histologically normal cartilage, was significantly higher than the damaged areas (ANOVA P< 0.0001). Furthermore, real time PCR showed that there was a significant difference in Collagen I expression between the damaged and macroscopically normal areas (p=0.04).

Conclusion: In AMOA there are distinct areas, demonstrating progressive cartilage loss. We conclude that in this phenotype the Collagen I increase, in areas of macroscopically and histologically normal cartilage, may represent very early changes of the cartilage matrix within the osteoarthritic disease process. This may be able to be used as an assay of early disease and as a therapeutic target for disease modification or treatment.

The aim of this study was to investigate the molecular features of progressive severities of cartilage damage, within the phenotype of Anteromedial Osteoarthritis of the Knee (AMOA).

Ten medial tibial plateau specimens were collected from patients undergoing unicompartmental knee replacements. The cartilage within the area of macroscopic damage was divided into equal thirds: T1(most damaged), to T3 (least damaged). The area of macroscopically undamaged cartilage was taken as a 4th sample, N. The specimens were prepared for histological (Safranin-O and H& E staining) and immunohistochemical analysis (Type I and II Collagen). Immunoassays were undertaken for Collagens I and II and GAG content. Real time PCR compared gene expression between areas T and N.

There was a decrease in OARSI grade across the four areas, with progressively less fibrillation between areas T1, T2 and T3. Area N had an OARSI grade of 0 (normal).

The GAG immunoassay showed decreased levels with increasing severity of cartilage damage (ANOVA P< 0.0001). There was no significant difference in the Collagen II content or gene expression between areas. The Collagen I immunohistochemistry showed increased staining within chondrocyte territorial areas in the undamaged region (N) and immunoassays showed that the Collagen I content of this macroscopically and histologically normal cartilage, was significantly higher than the damaged areas (ANOVA P< 0.0001). Furthermore, real time PCR showed that there was a significant increase in Collagen I expression in the macroscopically normal areas (p=0.04).

In AMOA there are distinct areas, demonstrating progressive cartilage loss. We conclude that in this phenotype the Collagen I increase, in areas of macroscopically and histologically normal cartilage, may represent very early changes of the cartilage matrix within the osteoarthritic disease process. This may be able to be used as an assay of early disease and as a therapeutic target for disease modification or treatment.