Utilization of bone morphogenetic protein receptors during chondrocyte maturation.
Cartilage from the upper, cephalic portion of embryonic chick sternums undergoes hypertrophy, while the lower, caudal portion of the sternum remains as cartilage. Bone morphogenetic proteins (BMPs) induce type X collagen (colX) in cultured upper but not lower sternal chondrocytes (LSCs). We have examined the utilization of BMP receptors (BMPRs) by upper sternal chondrocytes (USCs) and LSCs both by analyzing receptor expression and by overexpressing mutant BMPRs. Reverse-transcription polymerase chain reaction (RT-PCR) analyses indicate that both upper and lower chondrocytes produce messenger RNA (mRNA) for all three receptors: BMPR type IA (BMPR-IA), BMPR type IB (BMPR-IB), and BMPR type II (BMPR-II). Infection of USC with retroviral vectors expressing constitutively active (CA) BMPRs showed that CA-BMPR-IB, like exogenous BMP-4, induced both colX mRNA and elevated alkaline phosphatase (AP), while CA-BMPR-IA was markedly less potent. However, expression of activated receptors in LSC cultures resulted in only minimal induction of hypertrophic markers. Consistent with the results seen for CA receptors, dominant negative (DN) BMPR-IB blocked BMP-induced hypertrophy in USCs more effectively than DN-BMPR-IA. These results imply that the major BMPR required for BMP induction of chondrocyte hypertrophy is BMPR-IB, and that difference between permanent and prehypertrophic chondrocytes is not caused by absence of receptors required for BMP signaling.
Department of Biochemistry, School of Dental Medicine, University of Pennsylvania, Philadelphia, USA.
S W
SW
Volk
M
M
D'Angelo
D
D
Diefenderfer
P S
PS
Leboy
D000469:Alkaline Phosphatase / Q000096:biosynthesis; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D052004:Bone Morphogenetic Protein Receptors; D052005:Bone Morphogenetic Protein Receptors, Type I; D019485:Bone Morphogenetic Proteins / Q000235:genetics; D002352:Carrier Proteins; D002478:Cells, Cultured; D002642:Chick Embryo; D019902:Chondrocytes / Q000378:metabolism*; D003094:Collagen / Q000235:genetics; D004790:Enzyme Induction; D015870:Gene Expression; D005822:Genetic Vectors; D016296:Mutagenesis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000235:genetics / Q000378:metabolism*; D012190:Retroviridae; D015398:Signal Transduction; D013249:Sternum / Q000166:cytology / Q000196:embryology; D016212:Transforming Growth Factor beta; D000099176:Noggin Protein
D000469:Alkaline Phosphatase; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D052004:Bone Morphogenetic Protein Receptors; D052005:Bone Morphogenetic Protein Receptors, Type I; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D003094:Collagen; D017346:Protein Serine-Threonine Kinases; D011506:Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D016212:Transforming Growth Factor beta; D000099176:Noggin Protein