Fig. 3.

In vivo remodeling and vascularization of late hypertrophic cartilage implants. (A) The observed remodeling resembles the temporal and spatial changes indicative of ongoing endochondral ossification. Hypertrophic chondrocytes located in the bony collar (BC) synthesized MMP13, which is known to prepare the ECM for vascular invasion during endochondral ossification. (B and C) Newly formed vessels, identified by CD31+ endothelial cells, penetrated the outer matrix and reached the inner core in close proximity to the cartilaginous areas undergoing remodeling (arrows). (D and E) The cartilaginous regions were colonized by TRAP-positive cells synthesizing MMP9. (F) These regions were also positive for the DIPEN, which is produced by MMP-mediated cleavage of aggrecan. (Scale bar: 100 μm.)