Distribution of the Transcription Factors Sox9, AP-2, and [Delta]EF1 in Adult Murine Articular and Meniscal Cartilage and Growth Plate

Abstract

the development, maintenance, and repair of cartilage tissues. Matrix molecule synthesis is generally regulated by the rate of gene transcription determined by DNA transcription factors. We have shown that transcription factors Sox9, AP-2, and [delta]EF1 are able to alter the rate of CD-RAP transcription in vitro: Sox9 upregulates, AP-2 exhibits biphasic effects, and [delta]EF1 represses expression of the CD-RAP gene. To correlate these in vitro activities in vivo, transcription factors were co-immunolocalized with ECM proteins in three different cartilage tissues in which the rates of biosynthesis are quite different: articular, meniscal, and growth plate. Immunoreactivities of type II collagen and CD-RAP were higher in growth plate than in either the articular or meniscal cartilages and correlated positively with Sox9 protein. Sox9 staining decreased with hypertrophy and was low in articular and meniscal cartilages. In contrast, AP-2 and [delta]EF1 were low in proliferating chondrocytes but high in lower growth plate, articular, and meniscal cartilages. This increase was also accompanied by intense nuclear staining. These immunohistochemical results are the first to localize both [delta]EF1 and AP-2 to adult articular, meniscal, and growth plate cartilages and provide in vivo correlation of previous molecular biological studies.

A promoter element of the CD‐RAP gene is required for repression of gene expression in non‐cartilage tissues in vitro and in vivo

“…Immunohistochemistry for CD-RAP and C/EBPa, b, d confirmed this expression pattern in vivo (data not shown). C/EBPb and C/EBPd were detected in the lower half of the growth plate where CD-RAP expression begins to decline [Davies et al, 2002]. C/EBPa was not detected (data not shown).…”

Induction of original phenotype of human immortalized chondrocytes: A quantitative gene expression analysis

“…This is confirmed by the expression of cartilage markers and by the presence of specific transcription factors such as Sox-9 and Egr-1 which are known to be involved in the modulation of chondrocyte phenotypic gene expression. Sox-9 is a member of the family of Sox (Sry-type highmobility group box transcription factor) genes and contains a high mobility group DNA-binding domain (33). It has been demonstrated to play an essential role in the commitment of mesenchymal cells to the chondrogenic lineage and in the process of chondrocyte differentiation.…”

Association of the –381T/C promoter variation of the brain natriuretic peptide gene with low bone-mineral density and rapid postmenopausal bone loss

“…Predictive analysis of binding motifs for transcription factors using the MatInspector pro- gram revealed that the -381T/C variation is located within the consensus binding sequence of δ-crystallin/E2-box factor 1 (δ-EF1; GGACACCTGGA) and upstream stimulatory factor (ACACCTGG), both of which contain an E-box binding element (CAnnTG) inside them (Sekido et al 1994;Dillner and Sanders 2002;Viollet et al 1996). Because δ-EF1 is an important transcription factor that distributes in many organs including connective tissues of the skeletal system (Davies et al 2002;Funahashi et al 1993;Terraz et al 2001;Sooy and Demay 2002), it regulates not only tissuespecific expression of the crystalline gene in the lens, but also many genes including collagens and osteocalcin genes important for bone and cartilage development and maintenance (Funahashi et al 1993;Terraz et al 2001;Sooy and Demay 2002). Altered promoter function could account for the different clinical features of bone mass in individuals, which should be examined in the future by means of a binding assay for each transcription factor, or by a promoter activity test using reporter constructs, for example.…”