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

自分泌和局部因素可能在胚胎期骨骼组织的发育和生长中起关键作用。我们研究了TGF-β对从胎鼠中分离的下颌髁突软骨器官培养物的影响。当它们与TGF-β培养时，新的成软骨细胞发育，随后成熟，显示肥大和软骨特异性蛋白聚糖形成的迹象。DNA合成迅速增加，在加入TGF-β后2天达到最大值。放射自显影显示高标记细胞局限于前软骨祖细胞区。然后在2天后将标记转移到成熟的软骨细胞。相反，TGF-β降低碱性磷酸酶活性和^<45>Ca摄取。加入bFGF后获得类似的结果。这些发现表明，局部因子作为调节剂的软骨祖细胞的生长和分化的软骨表型的表达。我们成功地纯化从胎牛软骨的软骨特异性生长调节因子，在分化的软骨细胞的生长调节功能。我们将这一原理命名为“Chondromodulin-I（ChMI）”。成熟ChM-I由122个氨基酸组成，具有3个糖基化位点，并编码为较大前体的C-末端部分。前体有335个氨基酸。成熟的ChM-I刺激培养的生长板软骨细胞的DNA合成和蛋白聚糖合成。在bFGF的存在下，ChM-I协同刺激培养的软骨细胞的生长。这些发现表明基质的功能组分参与细胞生长和分化的生理调节。除了内分泌、旁分泌和自分泌途径外，细胞与基质吸附因子（如ChM-I）的相互作用可称为“自基质作用”。

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".