Disrupted type II collagenolysis impairs angiogenesis, delays endochondral ossification and initiates aberrant ossification in mouse limbs
SJ Gauci, SB Golub, L Tatarczuch, E Lee, D Chan, NC Walsh, CB Little, H Stanton, Z Lokmic, NA Sims, EJ Mackie, AJ Fosang
Matrix Biology | ELSEVIER | Published : 2019
Cartilage remodelling and chondrocyte differentiation are tightly linked to angiogenesis during bone development and endochondral ossification. To investigate whether collagenase-mediated cleavage of the major cartilage collagen (collagen II) plays a role in this process, we generated a knockin mouse in which the mandatory collagenase cleavage site at PQG775↓776LAG, was mutated to PPG775↓776MPG (Col2a1Bailey). This approach blocked collagen II cleavage, and the production of putative collagen II matrikines derived from this site, without modifying matrix metalloproteinase expression or activity. We report here that this mouse (Bailey) is viable. It has a significantly expanded growth plate a..View full abstract
Awarded by National Health and Medical Research Council of Australia
Awarded by Australian Research Council
This work was supported by the National Health and Medical Research Council of Australia (170207, 400057, 1002871, 607385), the Australian Research Council (DP130104083), Pfizer, USA and the Victorian Government's Operational Infrastructure Support Program.