The use of in vitro models for investigating the response of fibrous joints to tensile mechanical stress

Abstract

To clarify the role of mechanical deformation in the remodeling of fibrous joints, organ culture systems have been developed to apply mechanical stress to cranial sutures under controlled experimental conditions. Tensile mechanical stress applied to cranial sutures from newborn rabbits produces a two- to threefold increase in protein synthesis and a twofold increase in collagen synthesis that can be detected within 6 hours. There is also a threefold increase in the DNA content of the sutures after 48 hours. Under normal conditions sutural fibroblasts synthesize type I collagen but respond to tensile deformation by synthesizing significant amounts of type III collagen. This suggests that the biomechanical environment of a connective tissue cell is an important determinant of the collagen type synthesized. However, the effect is likely to be an indirect one by virtue of its influence on the metabolic activity of the cells. Mechanically activated cells do not preferentially synthesize structural proteins, since mechanical stress stimulates the synthesis not only of structural macromolecules but also of the enzymes responsible for their specific hydrolysis. This is not accompanied by increased degradation, however, perhaps because the metalloproteinase inhibitor TIMP synthesized by the tissues is also increased. Confluent rabbit and mouse periosteal fibroblasts synthesize and release into the culture medium factors that can inhibit bone cell proliferation and stimulate bone resorption in vitro. It seems likely that further investigation of the interaction between fibroblasts and osteoblasts at the bone—fibrous tissue interface will require a reassessment of current thinking concerning the mechanisms regulating sutural osteogenesis.