Bi-directional modulation of cellular interactions in an in vitro co-culture model of tendon-to-bone interface

Abstract

Objectives: This work aimed at studying in vitro interactions between human tendonâ derived cells (hTDCs) and preâ osteoblasts (preâ OBs) that may trigger a cascade of events involved in enthesis regeneration.

Materials and methods

The effect of 5 osteogenic medium (OM) conditions over the modulation of hTDCs and preâ OBs towards the tenogenic and osteogenic phenotypes, respectively, was studied. Three different medium conditions were chosen for subsequently establishing a direct coâ culture system in order to study the expression of bone, tendon and interfaceâ related markers.

Results

A higher matrix mineralization and ALP activity was observed in coâ cultures in the presence of OM. Higher transcription levels of boneâ (ALPL, RUNX2, SPP1) and interfaceâ related genes (ACAN, COMP) were found in coâ cultures. The expression of aggrecan was influenced by the presence of OM and cellâ cell interactions occurring in coâ culture.

Conclusions

The present work assessed both the influence of OM on cell phenotype modulation and the importance of coâ culture models while promoting cellâ cell interactions and the exchange of soluble factors in triggering an interfaceâ like phenotype to potentially modulate enthesis regeneration.