title: Histochemical aspects of the vascular invasion at the erosion zone of the epiphyseal cartilage in MMP-9-deficient mice.
abstract: We have histologically examined vascular invasion and calcification of the hypertrophic zone during endochondral ossification in matrix metalloproteinase (MMP)-9 deficient (MMP-9-/-) mice and in their littermates at 3 days, 3 weeks and 6 weeks after birth. Capillaries and osteoclasts at the chondro-osseous junction showed an intense MMP-9 immunopositivity, suggesting that they recognize chemical properties of cartilaginous matrices, and then release MMP-9 for cartilage degradation. CD31-positive capillaries and tartrate-resistant acid phosphatase-reactive osteoclasts could be found in the close proximity in the region of chondro-osseous junction in MMP-9-/- mice, while in wild-type mice, vascular invasion preceded osteoclastic migration into the epiphyseal cartilage. Although MMP-9-/- mice revealed larger hypertrophic zones, the index of calcified area was significantly smaller in MMP-9-/- mice. Interestingly, the lower layer of the MMP-9-/- hypertrophic zone showed intense MMP-13 staining, which could not be observed in wild-type mice. This indicates that MMP-13 may compensate for MMP-9 deficiency at that specific region, but not to a point at which the deficiency could be completely rescued. In conclusion, it seems that MMP-9 is the optimal enzyme for cartilage degradation during endochondral ossification by controlling vascular invasion and subsequent osteoclastic migration.
authors.affiliation: Division of Reconstructive Surgery for Oral and Maxillofacial Region, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. t-kojima@dent.niigata-u.ac.jp
authors.forename: Taku
authors.initials: T
authors.lastname: Kojima
authors.forename: Tomoka
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Paulo Henrique Luiz
authors.initials: PH
authors.lastname: de Freitas
authors.forename: Tomomaya
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Muneteru
authors.initials: M
authors.lastname: Sasaki
authors.forename: Keisuke
authors.initials: K
authors.lastname: Horiuchi
authors.forename: Hiromi
authors.initials: H
authors.lastname: Hongo
authors.forename: Tamaki
authors.initials: T
authors.lastname: Yamada
authors.forename: Naoko
authors.initials: N
authors.lastname: Sakagami
authors.forename: Naoaki
authors.initials: N
authors.lastname: Saito
authors.forename: Michiko
authors.initials: M
authors.lastname: Yoshizawa
authors.forename: Tadaharu
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Takeyasu
authors.initials: T
authors.lastname: Maeda
authors.forename: Chikara
authors.initials: C
authors.lastname: Saito
authors.forename: Norio
authors.initials: N
authors.lastname: Amizuka
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002113:Calcification, Physiologic; D002465:Cell Movement; D019902:Chondrocytes / Q000166:cytology / Q000201:enzymology; D042783:Endothelial Cells / Q000166:cytology* / Q000201:enzymology; D015870:Gene Expression; D006132:Growth Plate / Q000098:blood supply* / Q000166:cytology* / Q000201:enzymology / Q000254:growth & development; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000172:deficiency / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic; D010010:Osteoclasts / Q000166:cytology* / Q000201:enzymology; D010012:Osteogenesis
chemical_list: D053509:Matrix Metalloproteinase 13; D020780:Matrix Metalloproteinase 9