Abstract
Novel sulphation motifs within the glycosaminoglycan (GAG) chain structure of chondroitin sulphate (CS)- containing s are associated with sites of growth and differentiation in many biological systems where they function as molecular recognition sites involved in the binding, sequestration or presentation of soluble signalling molecules (e.g. growth factors, cytokines, morphogens). The specific sulphation motifs on CS identified by monoclonal antibodies 3-B-3(-), 4-C-3 and 7-D-4 are also associated with distinct cohorts of cells in areas of tissue morphogenesis in human foetal knee joint development. We hypothesize that such motifs may have roles to play in the regulation of proliferative/differentiative events during tissue morphogenesis. In the present investigation we have examined the distribution of these CS motifs within the rudiment cartilage, stromal connective tissues surrounding the rudiment cartilages and developing growth plates of the human foetal knee joint. These CS motifs had broad, overlapping distributions throughout the differentiating connective tissues undergoing morphogenesis and after joint cavitation were localised very specifically to the rudiment cartilage destined to form the permanent articular cartilage postnatally, and to the terminally differentiated chondrocytes and calcified cartilage-bone interface in the growth plate cartilages. The overlapping distributions of these molecules within the presumptive articular cartilage, prior to secondary ossification, suggests that they participate in early signalling events involved in tissue development and indicates that the cells within this zone are phenotypically distinct from those of the underlying rudiment cartilage.
Highlights
The knee is the largest diarthrodial joint in the human body
In the present study we have extended earlier studies on the chondroitin sulphate (CS) motifs in joint development by showing that they are present in areas of tissue morphogenesis associated with bone development
The rudiments are formed from condensations of chondroblastic progenitor cells of mesenchymal origin which proliferate, differentiate and lay down an ECM rich in type II collagen, aggrecan and perlecan by a process known as chondrogenesis
Summary
The knee is the largest diarthrodial (synovial) joint in the human body. It is a complex hinge joint consisting of articulations between the fibula and tibia, femur and tibia and the femur and patella [1]. An interzone between the tibial and femoral rudiments subsequently specifies the future joint line during the process of joint cavitation and serves as an important signalling centre, for members of the TGF-β (GDFs 5 and 6; BMPs 2, 3 and 4) and FGF superfamilies’, Wnt-4, -14 and -16 and BMP antagonists (Chordin and Noggin). This interzone precedes the formation of the synovial cavity and joint articulating surfaces. Differential synthesis of hyaluronan (HA) in the femoro-tibial inter zone results in an increase in HA concentration [3,9,10] which in combination with mechanical cues arising from muscular activity, reduces cohesion between the inter zone cells and propagates the separation of the presumptive articular surfaces [11]
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