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Postnatal Growth, Differentiation, and Aging of the Mouse Intervertebral Disc

Dahia, Chitra Lekha PhD*; Mahoney, Eric J. BA*; Durrani, Atiq A. MD*; Wylie, Christopher PhD†

doi: 10.1097/BRS.0b013e3181990c64
Basic Science

Study Design. This study follows postnatal intervertebral disc (IVD) growth and differentiation in the mouse.

Objective. To initiate use of the mouse as a model system for postnatal IVD differentiation and growth, and to serve as a basis for assaying changes caused by disease or genetic or experimental perturbation.

Summary of Background Data. Lower back pain caused by disc degeneration is one of the most common clinical conditions worldwide. There is currently no completely effective treatment, largely because of a lack of basic knowledge of the molecular and cellular controls of disc growth, differentiation, and maintenance after birth.

Methods. Conventional histology of decalcified IVDs, differential interference contrast, polarizing optics, immunocytochemistry, laser capture microscopy followed by molecular analysis of the dissected cells by reverse transcriptase polymerase chain reaction.

Results. There is a single postnatal growth spurt in the mouse IVD, between birth and 9 weeks of age. Cell proliferation was found in the nucleus pulposus (NP) and anulus fibrosus (AF) only until 3 weeks of age. Most of the postnatal growth of the IVD is due to accumulating extracellular matrix. NP cell numbers decline steadily after 2 weeks of age, because of apoptosis. Laser capture microscopy was used to dissect NP cells from the disc, and showed that these cells express markers of the embryonic notochord. The postnatal AF appears initially as a continuous structure surrounding the NP. This structure differentiates, during the first 2 postnatal weeks, to form the mineralized, but nonossified endplate over the surfaces of the vertebral growth plates, and the mature fibrous AF (fAF) passing between adjacent vertebrae. The fact that the mature fAF and the endplate form from an originally continuous layer of cells explains the anatomic relationship between these 2 structures, in which the fAF inserts into the vertebral endplate.

Conclusion. Growth of the IVD takes place during the first 9 postnatal weeks, although cell proliferation ceases after 3 weeks. After birth, the early postnatal IVD differentiates into 3 tissue types, the NP, the fAF between the vertebrae, and the mineralized endplates over the surfaces of the vertebrae.

This study describes the postnatal growth, differentiation, and ageing of the mouse lumbar intervertebral disc. Cell growth, proliferation, expression of molecular markers, and death, are assayed in the disc components with age. Differentiation of the anulus fibrosus is described.

From the Divisions of *Orthopaedic Surgery and †Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati OH.

Acknowledgment date: March 12, 2008. First revision date: July 18, 2008. Second revision date: October 7, 2008. Third revision date: November 20, 2008. Acceptance date: December 2, 2008.

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.

Atiq A. Durrani and Christopher Wylie contributed equally to this work.

Address correspondence and reprint requests to Christopher Wylie, PhD, Division of Developmental Biology, Cincinnati Children's Hospital Research Foundation, 3333 Burnet Ave., Cincinnati, OH 45229; E-mail: Christopher.Wylie@cchmc.org.

© 2009 Lippincott Williams & Wilkins, Inc.