| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Women’s Health Research Institute, Wyeth Research, Collegeville, Pennsylvania 19426
Address all correspondence and requests for reprints to: Julia Billiard, Ph.D., Women’s Health Research Institute, Wyeth Research, 500 Arcola Road, Collegeville, Pennsylvania 19426. E-mail: billiaj{at}wyeth.com.
Ror2 is an orphan receptor tyrosine kinase that plays crucial roles in developmental morphogenesis, particularly of the skeleton. We have identified human Ror2 as a novel regulator of canonical Wnt signaling in osteoblastic (bone-forming) cells with selective activities, enhancing Wnt1 but antagonizing Wnt3. Immunoprecipitation studies demonstrated physical interactions between human Ror2 and mammalian Wnt1 and Wnt3. Functionally, Ror2 antagonized Wnt1- and Wnt3-mediated stabilization of cytosolic ß-catenin in osteoblastic cells. However, Ror2 had opposing effects on a more distal step of canonical Wnt signaling: it potentiated Wnt1 activity but inhibited Wnt3 function as assessed by changes in Wnt-responsive reporter gene activity. Despite binding to Ror2, neither Wnt1 nor Wnt3 altered receptor activity as assessed by levels of Ror2 autophosphorylation. The ability of Ror2 to regulate canonical Wnt signaling in osteoblastic cells should have physiological consequences in bone, because Wnt signaling is known to modulate osteoblast survival and differentiation. Expression of Ror2 mRNA was highly regulated in a biphasic manner during human osteoblast differentiation, being virtually undetectable in pluripotent stem cells, increasing 300-fold in committed preosteoblasts, and disappearing again in osteocytes. Furthermore, Ror2 expression in osteoblasts was suppressed by the Wnt antagonist, secreted frizzled-related protein 1. The regulated expression of Ror2 during osteoblast differentiation, its inverse expression pattern with secreted frizzled-related protein 1, and its ability to modulate Wnt signaling in osteoblastic cells suggest that Ror2 may regulate bone formation.
This article has been cited by other articles:
 |
|
 |
|
  J. R. Kennerdell, R. D. Fetter, and C. I. Bargmann Wnt-Ror signaling to SIA and SIB neurons directs anterior axon guidance and nerve ring placement in C. elegans Development, November 15, 2009; 136(22): 3801 - 3810. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. van Amerongen and R. Nusse Towards an integrated view of Wnt signaling in development Development, October 1, 2009; 136(19): 3205 - 3214. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Caverzasio Non-Canonical Wnt Signaling: What Is Its Role in Bone? IBMS BoneKEy, March 1, 2009; 6(3): 107 - 115. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Henriquez, A. Webb, M. Bence, H. Bildsoe, M. Sahores, S. M. Hughes, and P. C. Salinas Wnt signaling promotes AChR aggregation at the neuromuscular synapse in collaboration with agrin PNAS, December 2, 2008; 105(48): 18812 - 18817. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Smerdel-Ramoya, S. Zanotti, L. Stadmeyer, D. Durant, and E. Canalis Skeletal Overexpression of Connective Tissue Growth Factor Impairs Bone Formation and Causes Osteopenia Endocrinology, September 1, 2008; 149(9): 4374 - 4381. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Smerdel-Ramoya, S. Zanotti, V. Deregowski, and E. Canalis Connective Tissue Growth Factor Enhances Osteoblastogenesis in Vitro J. Biol. Chem., August 15, 2008; 283(33): 22690 - 22699. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Raz, S. Stricker, E. Gazzerro, J. L. Clor, F. Witte, H. Nistala, S. Zabski, R. C. Pereira, L. Stadmeyer, X. Wang, et al. The mutation ROR2W749X, linked to human BDB, is a recessive mutation in the mouse, causing brachydactyly, mediating patterning of joints and modeling recessive Robinow syndrome Development, May 1, 2008; 135(9): 1713 - 1723. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Liu, J. F. Ross, P. V. N. Bodine, and J. Billiard Homodimerization of Ror2 Tyrosine Kinase Receptor Induces 14-3-3{beta} Phosphorylation and Promotes Osteoblast Differentiation and Bone Formation Mol. Endocrinol., December 1, 2007; 21(12): 3050 - 3061. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Green, T. Inoue, and P. W. Sternberg The C. elegans ROR receptor tyrosine kinase, CAM-1, non-autonomously inhibits the Wnt pathway Development, November 15, 2007; 134(22): 4053 - 4062. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Gazzerro, A. Smerdel-Ramoya, S. Zanotti, L. Stadmeyer, D. Durant, A. N. Economides, and E. Canalis Conditional Deletion of Gremlin Causes a Transient Increase in Bone Formation and Bone Mass J. Biol. Chem., October 26, 2007; 282(43): 31549 - 31557. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Rydziel, L. Stadmeyer, S. Zanotti, D. Durant, A. Smerdel-Ramoya, and E. Canalis Nephroblastoma Overexpressed (Nov) Inhibits Osteoblastogenesis and Causes Osteopenia J. Biol. Chem., July 6, 2007; 282(27): 19762 - 19772. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Liu, R. A. Bhat, L. M. Seestaller-Wehr, S. Fukayama, A. Mangine, R. A. Moran, B. S. Komm, P. V. N. Bodine, and J. Billiard The Orphan Receptor Tyrosine Kinase Ror2 Promotes Osteoblast Differentiation and Enhances ex Vivo Bone Formation Mol. Endocrinol., February 1, 2007; 21(2): 376 - 387. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Gazzerro, V. Deregowski, S. Vaira, and E. Canalis Overexpression of Twisted Gastrulation Inhibits Bone Morphogenetic Protein Action and Prevents Osteoblast Cell Differentiation in Vitro Endocrinology, September 1, 2005; 146(9): 3875 - 3882. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
