Display Settings:

Format

Send to:

Choose Destination
We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Osteoarthritis Cartilage. 2009 Jun;17(6):695-704. doi: 10.1016/j.joca.2008.11.003. Epub 2008 Nov 13.

A novel in vivo murine model of cartilage regeneration. Age and strain-dependent outcome after joint surface injury.

Author information

  • 1William Harvey Research Institute, Barts and the London Queen Mary's School of Medicine and Dentistry, Centre for Experimental Medicine and Rheumatology, London, UK.

Abstract

OBJECTIVES:

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.

CONCLUSION:

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.

Comment in

PMID:
19070514
[PubMed - indexed for MEDLINE]
PMCID:
PMC2706394
Free PMC Article

Images from this publication.See all images (6)Free text

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk