Molecular mechanisms that mediate mechanosensation during secondary chondrogenesis (921.9)

Abstract

The ability of cells to detect mechanical forces plays an essential role in generating the proper form and function of the craniofacial musculoskeletal system. One skeletal tissue that remains highly responsive to mechanical force is secondary cartilage, which develops along the surface of bone. Without appropriate mechanical stimulation, such as the forces that arise through motility of the embryo, secondary cartilage does not form, or degenerates. To elucidate how secondary cartilage is induced and maintained by mechanical force, we take advantage of the fact that secondary cartilage is closely associated with the specialized feeding of some species of birds. Duck utilize their jaws as a means to filter heavy sediment while chick peck at seed. Embryonic motility in duck induces secondary cartilage within the jaw adductor enthesis, creating a robust interface between tendon and bone on the coronoid process, and ultimately transducing the powerful muscle contractions needed to lift the jaw. In contrast, secondary cartilage is absent on the chick coronoid process. Our published and preliminary data lead us to hypothesize that species‐specific jaw anatomy generates dissimilar mechanical forces that differentially activate mechanosensitive Fibroblast Growth Factor and Calcium signaling pathways in duck versus chick, and instruct the duck jaw adductor enthesis to produce secondary cartilage. We employ gain‐ and loss‐of‐function approaches to modulate secondary chondrogenesis, as well as chick‐duck chimeras to test if chick cells can form secondary cartilage in a duck host environment. This research has the potential to translate into regenerative therapies to supplement surgical repair of torn and damaged muscle insertions.Grant Funding Source: Supported by NIH 5R01DE016402‐08