Molecular Parameters Indicating Adaptation to Mechanical Stress in Fibrous Connective Tissue

Abstract

The present study pursues the hypothesis that local compressive force and the occurrence of cartilage-specific transformation processes within the extracellular matrix of tendons and ligaments are directly correlated. We compare the pattern of certain marker molecules typical of (fibro)cartilage in select examples. Investigations are carried out of the extensor tendons of toes and fingers, the transverse ligament of the atlas, the transverse ligament of the acetabulum, and of the tendon of the superior oblique muscle and its trochlea. The marker molecules are detected with standardized immunohistochemical methods. The results show that certain molecules only occur under conditions of (relatively high) compressive stress, others being the result of tensile stress. The molecular spectrum of the molecules of the ECM allows qualifying conclusions as to the mechanical situation of a given part of the tissue. A quantifying statement about the intensity of compressive stress is not possible to make thus far, but the extension of the restructuring areas corresponds to the area of compressive stress. Depending on the intensity and duration of the local compressive strain, the molecules involved may be ordered chronologically according to their occurrence in the ECM. The glycosaminoglycans react at lower stress levels than the proteoglycans, which in turn react earlier than the collagens, especially with regard to the vanishing of type I collagen and the first occurrence of type II collagen. Of the glycosaminoglycans, dermatan sulfate and keratan sulfate occur first. These are detectable in virtually all cases. They are followed by chondroitin 4 sulfate. The last glycosaminoglycan, which occurs in already significantly fibrocartilaginous tissue, is chondroitin 6 sulfate. Under chronologically intensifying compressive stress in the increasingly fibrocartilaginous tissues, the proteoglycans versican and, to a lesser extent, tenascin--characteristic markers of fibrous tissue--can still be detected. However, their spatial expansion steadily decreases until they finally vanish. Contrastingly, aggrecan and link protein expression becomes increasingly prominent in such tissues. The spatial expansion of the adaptation zones in tendons and ligaments roughly corresponds with the zones subjected to compressive force; tensile stress alone does not result in a production of fibrocartilage. The questions asked at the beginning may thus be answered as follows: The molecular composition of the various fibrous connective tissues, such as tendons and ligaments, can be directly correlated with the respective tissue's mechanical function. As an expression of this regular interrelation, a ranking of certain ECM molecules may be set up that corresponds to the type, intensity, and duration of the mechanical stress. Grounded on this, it seems possible to prognosticate the occurrence of certain components in the ECM depending on the nature of the mechanical stress. The occurrence of certain molecules within the fibrocartilaginous tissue is of clinical importance in connection with various forms of rheumatoid arthritis and perhaps other diseases with an autoimmune-related etiology. Since a considerable part of the inflammatory destructions involved may at least indirectly result from autoimmune processes directed against the cartilage-type components of the ECM, every fibrocartilage constitutes a potential target to a certain degree. This applies particularly to those fibrocartilages whose ECM has a molecular composition closely resembling that of hyaline articular cartilage. Therefore, knowledge of the regional molecular composition allows a prediction of sites where clinical symptoms may occur in the course of rheumatoid arthritis.