title: Fibroblasts of spinal ligaments pathologically differentiate into chondrocytes induced by recombinant human bone morphogenetic protein-2: morphological examinations for ossification of spinal ligaments.
abstract: To elucidate the process of ossification in spinal ligaments, an aqueous solution containing recombinant human bone morphogenetic protein (BMP)-2 (40 micrograms/100 microL) was injected into murine ligamenta flava, and the ossification process was analyzed morphologically. In the control group, the solution administered lacked the protein; these flattened ligamentous fibroblasts possessing BMP receptors type IA and type II existed among type I collagen bundles. In the week immediately following the injection of BMP-2, ligamentous fibroblasts began to proliferate, differentiating into alkaline phosphatase-positive chondrocytes surrounded by an extracellular matrix composed of type I and II collagen. By the second week, differentiated chondrocytes of various stages were observed in type II collagen-rich matrix. These chondrocytes showed an abundance of BMP receptors type IA and II. The pathologically induced cartilage was resorbed by chondroclasts, permitting migration of blood vessels and osteogenic cells, as well as providing a site for endochondral ossification. By the third week, BMP-induced ossification had compressed the spinal cord, and by the sixth week, the ligamentous tissue had been almost completely replaced by bone. Ligamentous fibroblasts appeared to possess BMP receptors, as well as the potentiality to differentiate into chondrocytes. BMP receptors were upregulated during chondrification of ligamentous fibroblasts induced by exogenous BMP-2, suggesting that BMPs may play an important role in ossification of spinal ligaments.
authors.affiliation: First Department of Oral Anatomy, Niigata University School of Dentistry, Japan. pochi@dent.niigata-u.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Hoshi
authors.forename: N
authors.initials: N
authors.lastname: Amizuka
authors.forename: T
authors.initials: T
authors.lastname: Sakou
authors.forename: T
authors.initials: T
authors.lastname: Kurokawa
authors.forename: H
authors.initials: H
authors.lastname: Ozawa
mesh_terms: D000135:Acid Phosphatase / Q000032:analysis; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D055396:Bone Morphogenetic Protein 2; D052005:Bone Morphogenetic Protein Receptors, Type I; D052006:Bone Morphogenetic Protein Receptors, Type II; D019485:Bone Morphogenetic Proteins; D002114:Calcinosis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D002356:Cartilage / Q000473:pathology* / Q000648:ultrastructure; D002454:Cell Differentiation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000648:ultrastructure; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis; D017843:Ligamentum Flavum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008159:Lumbar Vertebrae / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000032:analysis; D017978:Receptors, Growth Factor / Q000032:analysis; D011994:Recombinant Proteins; D012260:Ribonucleases / Q000032:analysis; D000071681:Tartrate-Resistant Acid Phosphatase; D016212:Transforming Growth Factor beta
chemical_list: C525718:BMP2 protein, human; D015415:Biomarkers; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D007527:Isoenzymes; D017978:Receptors, Growth Factor; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D003094:Collagen; D017346:Protein Serine-Threonine Kinases; C498211:BMPR1A protein, human; C498218:BMPR2 protein, human; C498219:Bmpr2 protein, mouse; D052005:Bone Morphogenetic Protein Receptors, Type I; D052006:Bone Morphogenetic Protein Receptors, Type II; D012260:Ribonucleases; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase