title: Anti-catabolic effect of OP-1 in chronically compressed intervertebral discs.
abstract: Experimental animal models of disc degeneration have been used to assess the biomechanical behavior, biochemical composition, and biological changes in the intervertebral discs. The objective of our study was to evaluate the anabolic and anti-catabolic effects of intradiscal injection of Osteogenic Protein-1 (OP-1) by histology and immunohistochemistry in disc degeneration model. Thirty-four rats were divided into five groups: intact control; sham control; compressed nucleus pulposus (NP) injected with saline; and two OP-1 groups: COP-1 group (compression was continued after intradiscal OP-1 injection) and ROP-1 group (compression was released at the time of OP-1 injection). Anabolic and anti-catabolic effects of OP-1 were evaluated by histology and immunohistochemistry with the following antibodies: anti-pro- and anti-mature OP-1, anti-MMP-13, anti-aggrecanase, anti-substance P, anti-tumor necrosis factor-alpha (TNF-alpha), and anti-interleukin-1beta (IL-1beta). The OP-1 injection to the degenerative disc stimulated an anabolic response characterized by the restoration of the normal morphology of the disc, increased Safranin O staining in the NP, extention of the extracellular matrix, and stimulation of endogenous OP-1 synthesis in the NP, annulus fibrosis (AF), and end-plate. The anti-catabolic effect of OP-1 was documented by reduced immunostaining for aggrecanase, MMP-13, substance P, TNF-alpha, and IL-1beta. This study confirmed the anti-catabolic activity of OP-1 as demonstrated previously in human articular cartilage and provided critical evidence for the potential of OP-1 therapy in the treatment of disc degeneration. Because substance P is a neuropeptide linked with inflammation and pain, a reduction in the level of this protein may support our previously reported results on the effect of OP-1 on pain-related behavior.
authors.affiliation: Department of Biochemistry and Section of Rheumatology, Rush University Medical Center, 1735 W. Harrison, Chicago, Illinois 60612, USA. schubins@rush.edu
authors.forename: Susan
authors.initials: S
authors.lastname: Chubinskaya
authors.forename: Mamoru
authors.initials: M
authors.lastname: Kawakami
authors.forename: Lev
authors.initials: L
authors.lastname: Rappoport
authors.forename: Takuji
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Nami
authors.initials: N
authors.lastname: Migita
authors.forename: David C
authors.initials: DC
authors.lastname: Rueger
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D001696:Biomechanical Phenomena; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D004195:Disease Models, Animal; D010450:Endopeptidases / Q000276:immunology / Q000378:metabolism; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism; D007403:Intervertebral Disc / Q000378:metabolism* / Q000473:pathology; D007405:Intervertebral Disc Displacement / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000276:immunology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D000906:Antibodies; C525819:BMP7 protein, human; C525821:Bmp7 protein, rat; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D053583:Interleukin-1beta; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D013373:Substance P; D010450:Endopeptidases; D053509:Matrix Metalloproteinase 13; C083641:aggrecanase