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Intervertebral Disc Development Is Regulated by Wnt/β-catenin Signaling

Kondo, Naoki MD, PhD*,†; Yuasa, Takahito MD, PhD*,‡; Shimono, Kengo DDS, PhD*,§; Tung, Weien BS*,§; Okabe, Takahiro MD, PhD*,¶; Yasuhara, Rika DDS, PhD*; Pacifici, Maurizio PhD*,§; Zhang, Yejia MD, PhD; Iwamoto, Masahiro DDS, PhD*,§; Enomoto-Iwamoto, Motomi DDS, PhD*,§

doi: 10.1097/BRS.0b013e3181f52cb5
Basic Science

Study Design. Histologic analysis of intervertebral disc (IVD) in three types of transgenic mice.

Objective. To investigate the role of Wnt/β-catenin signaling in regulation of IVD development and organization.

Summary of Background Data. -catenin dependent Wnt signaling is one of the central regulators in cartilage development during limb skeletal formation. Little is known, however, about the physiologic relevance of this signaling pathway to IVD development and organization.

Methods. Temporal-spatial distribution of Wnt/β-catenin signaling activity was examined in IVD using Wnt/β-catenin reporter (TOPGAL) mice. The structural changes in the mouse IVD components such as the nucleus pulposus (NP), endplate (EP), annulus fibrosus (AF), and the growth plate (GP) of the vertebral body were analyzed after transient activation of Wnt/β-catenin signaling or deletion of β-catenin in the mice.

Results. Activity of Wnt/β-catenin signaling was high in EP, AF, and GP in the embryonic stages and decreased at the postnatal stage; it was undetectable in the embryonic NP but upregulated after birth. The transient activation of Wnt/β-catenin signaling caused severe deterioration of the GP and the AF, whereas deficiency of β-catenin accelerated bone formation in between EP and GP.

Conclusion. The findings in this study suggest that proper regulation of Wnt/β-catenin signaling is required for development and organization of IVD.

Temporal-spatial manner regulation of Wnt/β-catenin signaling activity was demonstrated during intervertebral disc (IVD) organization. Dysregulation of Wnt/β-catenin signaling caused a marked deterioration of IVD structures, indicating that proper balance of this signaling is required for development and organization of the IVD.

*Department of Orthopaedic Surgery, Thomas Jefferson University, College of Medicine, Philadelphia, PA

Department of Orthopaedic Surgery, Niigata University, Niigata, Japan

Department of Orthopaedic Surgery, Juntendo University, Tokyo, Japan

§Division of Orthopaedc Surgery, The Children's Hospital of Philadelphia, Philadelphia, PA

Department of Surgery and Bioengineering, Tokyo University, Tokyo Japan

Departments of Orthopedic Surgery and Physical Medicine and Rehabilitation, Rush University Medical Center, Chicago, IL.

Address correspondence and reprint requests to Masahiro Iwamoto, DDS, PhD, Division of Orthopaedic Surgery, The Children's Hospital of Philadelphia, ARC902, 3615 Civic Center Blvd, Philadelphia, PA 19104; E-mail:

Acknowledgment date: May 6, 2009. Revision date: May 19, 2010. Accepted date: August 2, 2010.

The manuscript submitted does not contain information about medical device(s)/drug(s).

No funds were received in support of this work. No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript.

© 2011 Lippincott Williams & Wilkins, Inc.