title: Altered distribution of bone matrix proteins and defective bone mineralization in klotho-deficient mice.
abstract: In an attempt to identify the histological properties of the klotho-deficient (kl/kl) bone matrix, bone mineralization and the localization of Ca(2+)-binding bone matrix proteins - osteocalcin, dentin matrix protein-1 (DMP-1) and matrix Gla protein (MGP) - were examined in kl/kl tibiae. While a widespread osteocalcin staining could be verified in the wild-type bone matrix, localization of the same protein in the kl/kl tibiae seemed rather restricted to osteocytes with only a faint staining of the whole bone matrix. In wild-type mice, MGP immunoreactivity was present at the junction between the epiphyseal bone and cartilage, and at the insertion of the cruciate ligaments. In kl/kl mice, however, MGP was seen around the cartilaginous cores of the metaphyseal trabeculae and in the periphery of some cells of the bone surface. DMP-1 was identified in the osteocytic canalicular system of wild-type tibiae, but in the kl/kl tibiae this protein was mostly found in the osteocytic lacunae and in the periphery of some cells of the bone surface. Mineralization of the kl/kl bone seemed somewhat defective, with broad unmineralized areas within its matrix. In these areas, mineralized osteocytes along with their lacunae and osteocytic cytoplasmic processes were found to have intense osteocalcin and DMP-1 staining. Taken together, it might be that the excessive production of Ca(2+)-binding molecules such as osteocalcin and DMP-1 by osteocytes concentrates mineralization around such cells, disturbing the completeness of mineralization in the kl/kl bone matrix.
authors: Department of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan; Department of Gerodontology, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan.
authors: Muneteru
authors: M
authors: Sasaki
authors: Tomoka
authors: T
authors: Hasegawa
authors: Tamaki
authors: T
authors: Yamada
authors: Hiromi
authors: H
authors: Hongo
authors: Paulo Henrique Luiz
authors: PH
authors: de Freitas
authors: Reiko
authors: R
authors: Suzuki
authors: Tomomaya
authors: T
authors: Yamamoto
authors: Chihiro
authors: C
authors: Tabata
authors: Satoru
authors: S
authors: Toyosawa
authors: Tsuneyuki
authors: T
authors: Yamamoto
authors: Kimimitsu
authors: K
authors: Oda
authors: Minqi
authors: M
authors: Li
authors: Nobuo
authors: N
authors: Inoue
authors: Norio
authors: N
authors: Amizuka
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005966:Glucuronidase / Q000172:deficiency / Q000235:genetics; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism; D000090265:Klotho Proteins; D008297:Male; D051379:Mice; D016253:Microscopy, Immunoelectron; D015675:Osteocalcin / Q000378:metabolism*; D010011:Osteocytes / Q000378:metabolism*; D053495:Osteopontin / Q000378:metabolism; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: C513308:Dmp1 protein, mouse; D016326:Extracellular Matrix Proteins; D007527:Isoenzymes; D015675:Osteocalcin; D053495:Osteopontin; D000469:Alkaline Phosphatase; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D005966:Glucuronidase; D000090265:Klotho Proteins
keywords: DMP-1; Klotho deficient mice; MGP; Osteocalcin; Osteocyte