Osteogenic Protein-1 (Osteogenic Protein-1/Bone... : Spine (original) (raw)
Basic Science
Osteogenic Protein-1 (Osteogenic Protein-1/Bone Morphogenetic Protein-7) Inhibits Degeneration and Pain-Related Behavior Induced by Chronically Compressed Nucleus Pulposus in the Rat
Kawakami, Mamoru MD*; Matsumoto, Takuji MD*; Hashizume, Hiroshi MD*; Kuribayashi, Koichi MD†; Chubinskaya, Susan PhD‡; Yoshida, Munehito MD*
From the Departments of *Orthopaedic Surgery, Wakayama Medical University, Wakayama, Japan, †Immunology and Pathology, Kansai College of Oriental Medicine, Osaka, Japan, and ‡Biochemistry and Section of Rheumatology, Rush University Medical Center, Chicago, IL.
Acknowledgment date: August 17, 2004. Revision date: October 7, 2004. Acceptance date: October 20, 2004.
Supported by a grant from the Japan Ministry of Education, Science, Sports and Culture, Grand-in-Aid for Scientific Research No. 13671536, 2001, and 2002.
The legal regulatory status of the device(s)/drug(s) that is/are the subject of this manuscript is not applicable in my country.
Institutional 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.
Address correspondence and reprint requests to Mamoru Kawakami, MD, PhD, Associate Professor, Department of Orthopaedic Surgery, Wakayama Medical University, 811-1, Kimiidera, Wakayama City, Wakayama 641-0012, Japan; E-mail [email protected]
Study Design.
To study the therapeutic efficacy of intradiscal injection of osteogenic protein-1 (OP-1) to reduce degeneration and associated discogenic pain.
Objective.
To evaluate if intradiscal injection of OP-1 can reverse disc degeneration and reduce hyperalgesia, a pain-related behavior.
Summary of Background Data.
We showed that induction of hyperalgesia was higher in rats exposed to compressed nucleus pulposus (NP). It has been reported that intradiscal injection of OP-1 stimulates synthesis of proteoglycans and collagen in normal intervertebral discs.
Methods.
Rats were divided into several groups. In the sham group, the rings of an Ilizarov-type apparatus were only applied to the tail without compression. In the compressed NP group, the apparatus was used to apply chronically compression to the tail. Four weeks after surgery, the NP group was subdivided into 3 groups: saline-treated and OP-1-treated, which was divided into 2 groups (i.e., the continuous compression OP-1 [COP-1] group, in which compression was continuously applied to the tail for 4 weeks after OP-1 treatment and the release compression OP-1 [ROP-1] group, in which compression was released at treatment. Either physiologic saline or OP-1 was injected into the instrumented NP. The treated NP was harvested and applied to the left lumbar nerve roots 4 weeks after injection. Hyperalgesia was measured up to 3 weeks after surgery. The degree of disc degeneration and the appearance of the extracellular matrix in the intervertebral discs were evaluated by histology.
Results.
Mechanical hyperalgesia was observed in the sham and saline groups, but not in the OP-1 treated group. In the saline group, NP cells became spindle-shaped. In the OP-1 group, the NP cells became swollen with vacuolated cytoplasm, and the content of the extracellular matrix was markedly increased.
Conclusion.
OP-1 injection into degenerative intervertebral disc resulted in the enhancement of the extracellular matrix and the inhibition of pain-related behavior.
© 2005 Lippincott Williams & Wilkins, Inc.