C-JUN AND JUND SUPPRESS MATURATION OF CHONDROCYTES

To analyze the function of AP-1 in cartilage formation, two types of p rimary chondrocytes, LS and US cells, were prepared from caudal (lower ) and cephalic (upper) regions of chicken sterna, respectively, All th e known components of chicken AP-1 (c-Fos, Fra-2, c-Jun, and JunD) wer e detected in both cell types, but the expression level of c-Jun was m uch higher in LS cells, which are rich in less mature chondrocytes tha n US cells. In the sterna, the expression level of c-Jun was also lowe r in the maturating or hypertropic chondrocytes than in proliferating chondrocytes. When US cells were treated with parathyroid hormone (PTH ), which prevented maturation as judged from the maturation-associated markers such as alkaline phosphatase and type X collagen, the express ion levels of c-Jun and JunD were constitutively elevated. To analyze the possible relationship between differentiation status and expressio n levels of Jun family proteins, they were exogenously introduced into the entire population of US cells within 2 days by using high titer, replication-competent retroviral vectors, Maturation-associated marker s in US cells were specifically lowered by exogenous expression of c-J un or JunD to similar levels to those of LS cells or US cells treated with PTH, When US cells were infected with the virus encoding a domina nt negative mutant of AP-1 (supJunD-1), maturation markers were modera tely increased 10 days after infection, The potent induction of alkali ne phosphatase activity in US cells by all-trans retinoic acid was ann ulled by exogenous expression of either c-Jun or JunD, These results s uggest that Jun family proteins negatively regulate the maturation pro cess of chondrocytes.