Temporal expression patterns of BMP receptors and collagen II (B) during periosteal chondrogenesis

Articular cartilage has a limited ability to repair itself. Periosteal grafts have chondrogenic potential and are used clinically to repair defects in articular cartilage. An organ culture model system for in vitro rabbit periosteal chondrogenesis has been established to study the molecular events of periosteal chondrogenesis in vitro. In this model, bone morphogenetic protein‐2 (BMP2) mRNA expression was found to be upregulated in the first 12 h. BMPs usually transduce their signals through a receptor complex that includes type II and either type IA or type IB BMP receptors. Receptors IA and IB play distinct roles during limb development. We have examined the temporal expression patterns for the mRNAs of these receptors using our experimental model. The mRNA expression patterns of these three BMP receptors differed from one another in periosteal explants during chondrogenesis. When these explants were cultured under chondrogenic conditions (agarose suspension with TGF‐β1 added to the media for the first 2 days), the expression of BMPRII mRNA and that of BMPRIA mRNA varied only slightly and persisted over a long time. In contrast, the expression of BMPRIB mRNA was upregulated within 12 h, peaked at day 5, and fell to a level that was barely detected beyond day 21. Moreover, the expression of BMPRIB mRNA preceded that of collagen type IIB mRNAs, a marker for matrix‐depositing chondrocytes. These data support a role for coordinate expression of BMP2 and its receptors early during periosteal chondrogenesis. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.

[1]  K. Miyazono,et al.  Characterization of type I receptors for transforming growth factor-beta and activin. , 1994, Science.

[2]  K. Miyazono,et al.  Activin receptor-like kinases: a novel subclass of cell-surface receptors with predicted serine/threonine kinase activity. , 1993, Oncogene.

[3]  M. Bolander,et al.  An effective method of completely removing contaminating genomic DNA from an RNA sample to be used for PCR , 1997, Molecular biotechnology.

[4]  R. Salter,et al.  The chondrogenic potential of free autogenous periosteal grafts for biological resurfacing of major full-thickness defects in joint surfaces under the influence of continuous passive motion. An experimental investigation in the rabbit. , 1986, The Journal of bone and joint surgery. American volume.

[5]  A. Economides,et al.  Morphogenesis of digits in the avian limb is controlled by FGFs, TGFbetas, and noggin through BMP signaling. , 1998, Developmental biology.

[6]  H. Moses,et al.  Cloning of a Novel Type II Serine/Threonine Kinase Receptor through Interaction with the Type I Transforming Growth Factor-β Receptor (*) , 1995, The Journal of Biological Chemistry.

[7]  J. Massagué,et al.  Characterization and cloning of a receptor for BMP-2 and BMP-4 from NIH 3T3 cells , 1994, Molecular and Cellular Biology.

[8]  K. Miyazono,et al.  Distinct spatial and temporal expression patterns of two type I receptors for bone morphogenetic proteins during mouse embryogenesis. , 1995, Endocrinology.

[9]  M. D’Angelo,et al.  Utilization of Bone Morphogenetic Protein Receptors During Chondrocyte Maturation , 2000, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[10]  M. Affolter,et al.  An absolute requirement for both the type II and type I receptors, punt and thick veins, for Dpp signaling in vivo , 1995, Cell.

[11]  J. Rubak Reconstruction of articular cartilage defects with free periosteal grafts. An experimental study. , 1982, Acta orthopaedica Scandinavica.

[12]  S. O’Driscoll,et al.  Articular cartilage regeneration using periosteum. , 1999, Clinical orthopaedics and related research.

[13]  K. Miyazono,et al.  Formation of hetero-oligomeric complexes of type I and type II receptors for transforming growth factor-beta. , 1994, The Journal of biological chemistry.

[14]  D. Saris,et al.  Initial evidence for the involvement of bone morphogenetic protein‐2 early during periosteal chondrogenesis , 1999, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[15]  D. Riddle,et al.  Identification of type I receptors for osteogenic protein-1 and bone morphogenetic protein-4. , 1994, The Journal of biological chemistry.

[16]  M. Bolander,et al.  Gene digging , 1998, Molecular biotechnology.

[17]  H. Jäck,et al.  Sequence of the rabbit glyceraldehyde-3-phosphate dehydrogenase-encoding cDNA. , 1995, Gene.

[18]  R. Salter,et al.  The induction of neochondrogenesis in free intra-articular periosteal autografts under the influence of continuous passive motion. An experimental investigation in the rabbit. , 1984, The Journal of bone and joint surgery. American volume.

[19]  H. Ichijo,et al.  Molecular cloning of rat bone morphogenetic protein (BMP) type IA receptor and its expression during ectopic bone formation induced by BMP. , 1994, Biochemical and biophysical research communications.

[20]  A. Poole,et al.  Chondrogenesis in periosteal explants. An organ culture model for in vitro study. , 1994, The Journal of bone and joint surgery. American volume.

[21]  V. Rosen,et al.  Purification and characterization of other distinct bone-inducing factors. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[22]  J. Massagué TGFβ Signaling: Receptors, Transducers, and Mad Proteins , 1996, Cell.

[23]  V. Rosen,et al.  Novel regulators of bone formation: molecular clones and activities. , 1988 .

[24]  J. Massagué,et al.  Serine/threonine kinase receptors: mediators of transforming growth factor beta family signals. , 1996, Cancer surveys.

[25]  G. Martin,et al.  FGF-4 and BMP-2 have opposite effects on limb growth , 1993, Nature.

[26]  K. Calame,et al.  Induction of c-myc transcription by the v-Abl tyrosine kinase requires Ras, Raf1, and cyclin-dependent kinases. , 1997, Genes & development.

[27]  S. Noji,et al.  Identification of a Human Type II Receptor for Bone Morphogenetic Protein-4 That Forms Differential Heteromeric Complexes with Bone Morphogenetic Protein Type I Receptors (*) , 1995, The Journal of Biological Chemistry.

[28]  V. Rosen,et al.  Recombinant human bone morphogenetic protein induces bone formation. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[29]  J. Massagué,et al.  Distinct roles of type I bone morphogenetic protein receptors in the formation and differentiation of cartilage. , 1997, Genes & development.

[30]  B. Hogan,et al.  Bone morphogenetic proteins: multifunctional regulators of vertebrate development. , 1996, Genes & development.

[31]  Teruhiko Yoshida,et al.  Cloning of human bone morphogenetic protein type IB receptor (BMPR-IB) and its expression in prostate cancer in comparison with other BMPRs , 1997, Oncogene.

[32]  S W O'Driscoll,et al.  The Repair of Major Osteochondral Defects in Joint Surfaces by Neochondrogenesis with Autogenous Osteoperiosteal Grafts Stimulated by Continuous Passive Motion: An Experimental Investigation in the Rabbit , 1986, Clinical orthopaedics and related research.