獣医学科

伊豆 弥生

イズ ヤヨイ  (Yayoi Izu)

基本情報

所属
日本獣医生命科学大学 獣医学部 獣医学科 教授

J-GLOBAL ID
202001015850591109
researchmap会員ID
R000006432

主要な論文

 43
  • Yayoi Izu, Sheila M. Adams, Brianne K. Connizzo, David P. Beason, Louis J. Soslowsky, Manuel Koch, David E. Birk
    Matrix Biology 2020年10月  査読有り筆頭著者責任著者
  • Yayoi Izu, Yoichi Ezura, Manuel Koch, David E Birk, Masaki Noda
    Cell and tissue research 364(3) 623-635 2016年6月  査読有り筆頭著者責任著者
    Bone formation is precisely regulated by cell-cell communication in osteoblasts. We have previously demonstrated that genetic deletion of Col6a1 or Col12a1 impairs osteoblast connections and/or communication in mice, resulting in bone mass reduction and bone fragility. Mutations of the genes encoding collagen VI cause Ullrich congenital muscular dystrophy (UCMD) and Bethlem myopathy (BM), which have overlapping phenotypes involving connective tissue and muscle. Recent studies have identified COL12A1 gene mutations in patients with UCMD- and BM-like disorders harboring no COL6 mutations, indicating the shared functions of these collagens in connective tissue homeostasis. The purpose of this investigation has been to test the hypothesis that collagens VI and XII have coordinate regulatory role(s) during bone formation. We analyzed the localization of collagens VI and XII relative to primary osteoblasts during osteogenesis. Immunofluorescence analysis demonstrated that collagens VI and XII colocalized in matrix bridges between adjacent cells during periods when osteoblasts were establishing cell-cell connections. Quantification of cells harboring collagen bridges demonstrated that matrix bridges were composed of collagens VI and XII but not collagen I. Interestingly, matrix bridge formation was impaired in osteoblasts deficient in either Col6a1 or Col12a1, suggesting that both collagens were indispensable for matrix bridge formation. These data demonstrate, for the first time, a functional relationship between collagens VI and XII during osteogenesis and indicate that a complex containing collagens VI and XII is essential for the formation of a communicating cellular network during bone formation.
  • Yayoi Izu, Yoichi Ezura, Manuel Koch, David E Birk, Masaki Noda
    Cell and tissue research 364(3) 677-679 2016年6月  査読有り
  • Yayoi Izu, Yoichi Ezura, Fumitaka Mizoguchi, Aya Kawamata, Tetsuya Nakamoto, Kazuhisa Nakashima, Tadayoshi Hayata, Hiroaki Hemmi, Paolo Bonaldo, Masaki Noda
    Tissue & cell 44(1) 1-6 2012年2月  査読有り
    Bone consists of type I collagen as a major protein with minor various matrix proteins. Type VI collagen is one of bone matrix proteins but its function is not known. We therefore examined the effects of type VI collagen deficiency on bone. 3D-μCT analysis revealed that type VI collagen deficiency reduced cancellous bone mass. Cortical bone mass was not affected. Type VI collagen deficiency distorted the shape of osteoblasts both in the cancellous bone and in the cambium layer of periosteal region. Furthermore, type VI collagen deficiency disorganized collagen arrangement. These data indicate that type VI collagen contributes to maintain bone mass.
  • Yayoi Izu, Mei Sun, Daniela Zwolanek, Guido Veit, Valerie Williams, Byeong Cha, Karl J Jepsen, Manuel Koch, David E Birk
    The Journal of cell biology 193(6) 1115-30 2011年6月13日  査読有り
    Differentiated osteoblasts are polarized in regions of bone deposition, demonstrate extensive cell interaction and communication, and are responsible for bone formation and quality. Type XII collagen is a fibril-associated collagen with interrupted triple helices and has been implicated in the osteoblast response to mechanical forces. Type XII collagen is expressed by osteoblasts and localizes to areas of bone formation. A transgenic mouse null for type XII collagen exhibits skeletal abnormalities including shorter, more slender long bones with decreased mechanical strength as well as altered vertebrae structure compared with wild-type mice. Col12a(-/-) osteoblasts have decreased bone matrix deposition with delayed maturation indicated by decreased bone matrix protein expression. Compared with controls, Col12a(-/-) osteoblasts are disorganized and less polarized with disrupted cell-cell interactions, decreased connexin43 expression, and impaired gap junction function. The data demonstrate important regulatory roles for type XII collagen in osteoblast differentiation and bone matrix formation.
  • Yayoi Izu, Heather L Ansorge, Guiyun Zhang, Louis J Soslowsky, Paolo Bonaldo, Mon-Li Chu, David E Birk
    Matrix biology : journal of the International Society for Matrix Biology 30(1) 53-61 2011年1月  査読有り
    Tendons are composed of fibroblasts and collagen fibrils. The fibrils are organized uniaxially and grouped together into fibers. Collagen VI is a non-fibrillar collagen expressed in developing and adult tendons. Human collagen VI mutations result in muscular dystrophy, joint hyperlaxity and contractures. The purpose of this study is to determine the functional roles of collagen VI in tendon matrix assembly. During tendon development, collagen VI was expressed throughout the extracellular matrix, but enriched around fibroblasts and their processes. To analyze the functional roles of collagen VI a mouse model with a targeted inactivation of Col6a1 gene was utilized. Ultrastructural analysis of Col6a1-/- versus wild type tendons demonstrated disorganized extracellular micro-domains and associated collagen fibers in the Col6a1-/- tendon. In Col6a1-/- tendons, fibril structure and diameter distribution were abnormal compared to wild type controls. The diameter distributions were shifted significantly toward the smaller diameters in Col6a1-/- tendons compared to controls. An analysis of fibril density (number/μm(2)) demonstrated a ~2.5 fold increase in the Col6a1-/- versus wild type tendons. In addition, the fibril arrangement and structure were aberrant in the peri-cellular regions of Col6a1-/- tendons with frequent very large fibrils and twisted fibrils observed restricted to this region. The biomechanical properties were analyzed in mature tendons. A significant decrease in cross-sectional area was observed. The percent relaxation, maximum load, maximum stress, stiffness and modulus were analyzed and Col6a1-/- tendons demonstrated a significant reduction in maximum load and stiffness compared to wild type tendons. An increase in matrix metalloproteinase activity was suggested in the absence of collagen VI. This suggests alterations in tenocyte expression due to disruption of cell-matrix interactions. The changes in expression may result in alterations in the peri-cellular environment. In addition, the absence of collagen VI may alter the sequestering of regulatory molecules such as leucine rich proteoglycans. These changes would result in dysfunctional regulation of tendon fibrillogenesis indirectly mediated by collagen VI.
  • Yayoi Izu, Fumitaka Mizoguchi, Aya Kawamata, Tadayoshi Hayata, Testuya Nakamoto, Kazuhisa Nakashima, Tadashi Inagami, Yoichi Ezura, Masaki Noda
    The Journal of biological chemistry 284(8) 4857-64 2009年2月20日  査読有り
    Renin angiotensin system (RAS) regulates circulating blood volume and blood pressure systemically, whereas RAS also plays a role in the local milieu. Previous in vitro studies suggested that RAS may be involved in the regulation of bone cells. However, it was not known whether molecules involved in RAS are present in bone in vivo. In this study, we examined the presence of RAS components in adult bone and the effects of angiotensin II type 2 (AT2) receptor blocker on bone mass. Immunohistochemistry revealed that AT2 receptor protein was expressed in both osteoblasts and osteoclasts. In addition, renin and angiotensin II-converting enzyme were expressed in bone cells in vivo. Treatment with AT2 receptor blocker significantly enhanced the levels of bone mass, and this effect was based on the enhancement of osteoblastic activity as well as the suppression of osteoclastic activity in vivo. These results indicate that RAS components are present in adult bone and that blockade of AT2 receptor results in alteration in bone mass.
  • Yayoi Izu, Satoshi Soeta, Shinji Kamiya, Toru R Saito, Shuji Yamano, Kazuyuki Taniguchi
    The Journal of veterinary medical science 67(9) 927-33 2005年9月  査読有り
    To investigate the distribution of the early stage chondrocytes during the formation and closure of epiphyseal growth plate (EGP) of the domestic cat, we examined the EGP of proximal tibiae by immunohistochemistry for type VI collagen. In the epiphyseal cartilage without the secondary ossification center (SOC) and EGP in newborn cats aged 1 and 10 days, type VI collagen-positive chondrocytes were located around the cartilage canals and articular surface. In the epiphyseal cartilage with the SOC and EGP in young cats aged 1 to 3 months, type VI collagen-positive chondrocytes were located in the upper resting zone of the EGP, and then increased throughout the resting zone along with maturation. In the adult cats with the partially closed EGP, type VI collagen-positive chondrocytes were distributed throughout the remaining EGP. These findings indicate that the early stage chondrocytes characterized with type VI collagen are continuously located in the EGP during maturation. In addition, the increase of the early stage chondrocytes and the decrease of the reserve chondrocytes in the EGP along with maturation may cause the cessation of the longitudinal growth of the EGP, and finally bring about the EGP closure.

MISC

 8

共同研究・競争的資金等の研究課題

 16