Isolated Chondrons: a Concept Comes of Age!

• The chondron concept was first introduced in 1925 by Benninghoff who used polarised light microscopy to show that the chondrocyte in hyaline cartilages was surrounded by a specialised region of matrix. However, this concept was not widely accepted a (the time, audit was until 1969 that Szirmai rekindled interest in the chondron concept. Using new histochemical interpretations coupled with rnicrochernical analysis, Szirmaishowed the "micro-world'"of'thechondron consisted of a fine collagenous ' 'perilacunar rim " surrounding aproteogycanrich ' lacunarspace". He also showed that chondrons could be extracted from horse nasal septum by high speed homogenisation and concluded that the chondron was mechanically robust and represented the primary functional and metabolic unit of hayline cartilages. Again the chondron concept was not widely embraced despite the rapid accumulation of data indicating common specialisations in the vicinity of hayline cartilage chondrocytes. In 1985, our own research on thestnicture and function of adult articular cartilage matrices led to the discovery of chondrons in the homogenate produced by slow speed homogenisation of canine tibial cartilage. The isolation of intact chondrons conclusively established the chondron as a microanatomical unit of adult articular car-tilage. Each chondron consisted of a chondrocyte intimately associated with a proteoglycan rich pericellular matrix which was surrounded by a densely compacted pericellular capsule composed of fine collagen species. We have now developed the isolated chondron as a model to study the natural interrelationship between the chon-drocyte and its pericellular microenvironment. Using morphological, histochemical, ultrastnictural, immunohistochemical, biochemical and metabolic techniques, we have successfully shown the isolated chondron is rich in chondroitin sulphate, keratan sulphate and hyaluronan glycosaminoglycans, collagen types II, VI, IX, and XI, and glycoproteins such as fibronectin and possibily laminin. Further studies of chondrons extracted from osteoarthritic cartilage suggest the chondron is remodelled during the degenerative process causing the pericellular microenvironment to expand and the chondrocyte to proliferate into the large clusters typical of osteoarthritic pathology. The data presented in this short review indicates that the chondron is a highly specialised microanatomical unit of adult articular cartilage and plays a fundamental role in the initiation and progression of degenerative arthritis. Future studies on the isolated chondron model will ensure a highly greater understanding of the role of the cellular microenvironment in articular cartilage biology and pathology. EVOLUTION OF THE CHOMDROH COHCEPT • The concept of the chondron was first introduced by Benninghoff (1) to describe the chondrocyte and its specialised microenvironment in a range of hyaline cartilages including adult articular cartilage. Each chondron was shown to consist of a chondrocyte,its 'lacunar space" and "perilacunar rim", and it was proposed that they represent the primary functional and metabolic unit responsible for cartilage matrix homeostasis (1,2). Some authors supported the concept of the chondron as a compression resistant, water filled "bladder" (3) but in general, the lack of correlation between Benninghoff's polarising microscope data and the accepted histochemical dogma of the period lead to the general dismissal of the chondron concept (4). In the 1960's however, Szirmai used new histochemical concepts and techniques in conjunction with microchemical analysis to demonstrate the heterogeneous distribution of proteoglycans and collagen in the matrix of horse nasal cartilage (2). He also suggested that chondrons were extremely mechanically robust structures, citing as evidence the presence of intact chondrons in the cartilagebone fracture plane of an accident victum (4) and in the sediment resulting from high speed homogenisation of horse nasal septum (2). The sum of these results prompted Szirmai to conclude that the chondron could be described as a separate anatomical, mechanical and physiological unit of cartilage (2,4). Yet despite Szirmai's excellent studies, little attention has been given to the subject since his retirement in the early 1970's (personal communication). Our discovery, in 1985, that intact chondrons could be extracted from adult canine tibial cartilage by slow speed homogenisation techniques has completely vindicated the conclusions of Benninghoff and Szirmai. This review briefly outlines the organisation of the pericellular microenvironment in adult articular cartilage and the development of the isolated chondron as a model to study cell-matrix interactions in articular cartilage health and disease, CHONDRONS: THE CHONDROCYTE AND ITS PERICELLULAR MICROEHVIRONMEMT IM HYALINE