Role of Osteoblast–Fibroblast Interactions in the Formation of the Ligament-to-Bone Interface

ABSTRACT: The anterior cruciate ligament (ACL) inserts into bone through a characteristic fibrocartilagenous interface, which is essential for load transfer between soft and hard tissues. This multi-tissue interface is lost post ACL reconstruction, and the lack of an anatomic fibrocartilage interface between graft and bone remains the leading cause of graft failure. Currently, the mechanism of interface formation is not known. As a fibrocartilage-like tissue is found within the bone tunnel post ACL reconstruction, we hypothesize that fibroblast–osteoblast interactions at the graft-to-bone junction play a role in fibrocartilage formation. To test this hypothesis, a co-culture model permitting osteoblast–fibroblast communications was used to determine the effects of heterotypic interactions on cell phenotype and the development of fibrocartilage-relevant markers in vitro. It was found that co-culture decreased cell proliferation and osteoblast-mediated mineralization, while inducing fibroblast-mediated mineralization. Moreover, the expression of interface-relevant markers such as collagen type II and aggrecan were detected. Our findings suggest that osteoblast–fibroblast interactions may lead to cell trans-differentiation and eventual fibrocartilage formation. These results provide new insight into the mechanism of fibrocartilage formation, which are critical for interface tissue engineering and achieving biologica