A novel in vivo murine model of cartilage regeneration. Age and strain-dependent outcome after joint surface injury.
OBJECTIVE
To generate and validate a murine model of joint surface repair following acute mechanical injury.


METHODS
Full thickness defects were generated in the patellar groove of C57BL/6 and DBA/1 mice by microsurgery. Control knees were either sham-operated or non-operated. Outcome was evaluated by histological scoring systems. Apoptosis and proliferation were studied using TUNEL and Phospho-Histone H3 staining, respectively. Type II collagen neo-deposition and degradation were evaluated by immunostaining using antibodies to the CPII telopeptide and C1,2C (Col2-3/4Cshort), respectively. Aggrecanases and matrix metalloproteinases (MMPs) activity were assessed by immunostaining for TEGE(373) and VDIPEN neo-epitopes.


RESULTS
Young 8-week-old DBA/1 mice displayed consistent and superior healing of the articular cartilage defect. Age-matched C57BL/6 mice repaired poorly and developed features of osteoarthritis (OA). Compared to C57BL/6, DBA/1 mice displayed a progressive decline of chondrocyte apoptosis, cell proliferation within the repair tissue, persistent type II collagen neo-deposition, less type II collagen degradation, less aggrecanases and more MMP-induced aggrecan degradation. Eight-month-old DBA/1 mice failed to repair, but, in contrast to age-matched C57BL/6 mice, developed no signs of OA.


CONCLUSIONS
We have generated and validated a murine model of cartilage regeneration in which the outcome of joint surface injury is strain and age dependent. This model will allow, for the first time, the dissection of different pathways involved in joint surface regeneration in adult mammals using the powerful technology of mouse genetics.
Eltawil
N M
NM
William Harvey Research Institute, Barts and the London Queen Mary's School of Medicine and Dentistry, Centre for Experimental Medicine and Rheumatology, London, UK.
De Bari
C
C
Achan
P
P
Pitzalis
C
C
Dell'accio
F
F
D000367:Age Factors; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001169:Arthritis, Experimental / Q000473:pathology* / Q000503:physiopathology; D002358:Cartilage, Articular / Q000293:injuries / Q000378:metabolism* / Q000503:physiopathology; D055513:Connective Tissue Growth Factor / Q000378:metabolism*; D007718:Knee Injuries / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D020370:Osteoarthritis, Knee / Q000473:pathology* / Q000503:physiopathology
D055513:Connective Tissue Growth Factor; D020782:Matrix Metalloproteinases