Bone morphogenetic protein‐7 in growth‐plate chondrocytes: Regulation by retinoic acid is dependent on the stage of chondrocyte maturation

Abstract

Although the bone morphogenetic proteins stimulate chondrogenesis, little is known regarding their expression and regulation in growth-plate chondrocytes. The expression of bone morphogenetic protein-7 was examined in chick growth-plate chondrocyte cultures. Low basal levels of bone morphogenetic protein-7 mRNA and protein expression were stimulated by increasing doses of all-trans retinoic acid, a metabolite of vitamin A. The addition of 10 microM retinoic acid resulted in approximately a 6-fold increase in bone morphogenetic protein-7 mRNA levels. In contrast, other growth regulators, including basic fibroblast growth factor, transforming growth factor-beta, vitamin D, bone morphogenetic protein-6, bone morphogenetic protein-7, and parathyroid hormone-related peptide, did not alter bone morphogenetic protein-7 transcript levels. The increase in bone morphogenetic protein-7 transcripts, although present at 6 hours, was maximal following a 12-hour exposure to retinoic acid. Retinoic acid induction of bone morphogenetic protein-7 transcript levels was dependent on protein synthesis because the induction could be blocked by cyclohexamide. In maturationally distinct subpopulations of chondrocytes separated by countercurrent centrifugal elutriation, retinoic acid markedly induced bone morphogenetic protein-7 mRNA levels in the least differentiated chondrocytes but had no effect in the most terminally differentiated hypertrophic chondrocytes. Immunohistochemical localization of bone morphogenetic protein-7 demonstrates its expression throughout the developing and adolescent growth plate consistent with the constitutive pattern of expression seen in isolated chondrocytes. The addition of exogenous bone morphogenetic protein-7 to chondrocyte cultures stimulated maturation in undifferentiated chondrocyte populations. The data support a role for bone morphogenetic protein-7 as an autocrine regulator of chondrocyte maturation in the growth plate. Regulation of bone morphogenetic protein-7 by retinoic acid may be important in normal growth and development as well as in pathologic conditions of an excess or deficiency of vitamin A.

Comparative analysis of zebrafish bone morphogenetic proteins 2, 4 and 16: molecular and evolutionary perspectives

“…On the other hand, RA was described as downregulating the expression of BMP7 in rats with cleft palate [89], and expression of BMP2 and BMP4 was also observed to decrease in MG63 cells after RA treatment [90]. Contradictory results for the RA regulation of BMP genes suggest a context-dependent effect of the morphogen and is most likely related to the presence/absence of co-regulators [91][92][93].…”

Endogenous BMP-4 and BMP-7 Gene Expression in Cd-1 Mouse During Chondrogenesis Induced by Bovine Bone Morphogenetic Protein Implantation

“…The initiation of chondrogenesis could also be observed in in situ hybridization as the transcription of both endogenous BMP-4 and BMP-7 genes. BMP-4 and BMP-7 have been reported to be involved in embryonic chondrogenesis, 6 the process of which seems to be similar to the chondrogenesis induced here by bovine BMP. Our results also showed that the higher the number of typical chondroblasts, the higher the expression of BMP-4 and BMP-7.…”

The 5′ Flanking Region of the Human Bone Morphogenetic Protein-7 Gene

“…Indeed, WT-1 directed BMP-7 expression in situ may be necessary for proper mesenchymal cell condensation and subsequent epithelialization (33). Therefore, the The presence of several glucocorticoid concensus sequences (PPAR/RXR, GR/PR) lends credence to the fact that both vitamin D3 and retinoic acid can upregulate expression of endogenous BMP-7 in mouse autopods (38) and growth plate chondrocytes (39).…”

“…A variety of other agents including prostaglandin E 1 and F 2␣ , and (24-25) vitamin D3 had no effect on either cell line. Upregulation of BMP-7 by prostaglan- din E 2 in cortical and cancellous bone (40) and by retinoic acid (39) has been reported. BMP-7, which has been suggested to have an autoregulatory activity in the embryonic nephrogenic mesenchyme (33), did not significantly induce luciferase expression from p3.3.…”