Role of local factors on growth and aging of mandibular condylar cartilage

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Autocrineand local factors may play key roles in the development and growth of skeletal tissues in fetal stage. We examined the effects of TGF-beta on organ cultures of mandibular condylar cartilage, isolated from fetal mice. When they were cultured with TGF-beta, new chondroblasts developed which subsequently matured showing signs of hypertrophy and formation of cartilage-specific proteoglycans. DNA synthesis increased rapidly, reaching a maximum 2 days after addition of TGF-beta. Autoradiography showed that highly labeled cells were confined to the precartilage progenitor zone. The label was then transferred to matured chondrocytes after 2 days. In contrast, TGF-beta decreased alkaline phosphatase activity and ^<45>Ca uptake. Similar results were obtained following the addition of bFGF. These findings indicated that local factors are functioning as regulators of chondroprogenitor cell growth and expression of the differentiated cartilage phenotype.We succeeded in purification from fetal bovine cartilage of a cartilage-specific growth modulating factor that functions in growth regulation of the differentiated chondrocytes. We named this principle "Chondromodulin-I (ChMI). Mature ChM-I consists of 122 amino acids with 3 glycosylation sites and is coded as the C-terminal part of a larger precursor. The precursor has 335 amino acids. Mature ChM-I stimulates both DNA synthesis and proteoglycan synthesis of cultured growth-plate chondrocytes. In the presence of bFGF, ChM-I synergistically stimulates the growth of cultured chondrocytes. These findings indicate that functional components of the matrix participate in physiological regulation of cellular growth and differentiation. In addition to endocrine, paracrine, and autocrine routes, cellular interaction with matrix-adsorbed factors such as ChM-I could be called "auto-matrierine".