Skeletal overgrowth in transgenic mice that overexpress brain natriuretic peptide

Michio Suda, Yoshihiro Ogawa, Kiyoshi Tanaka, Naohisa Tamura, Akihiro Yasoda, Toshiya Takigawa, Masahiro Uehira, Hirofumi Nishimoto, Hiroshi Itoh, Yoshihiko Saito, Kohei Shiota, Kazuwa Nakao

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

Longitudinal bone growth is determined by the process of endochondral ossification in the cartilaginous growth plate, which is located at both ends of vertebrae and long bones and involves many systemic hormones and local regulators. Natriuretic peptides organize a family of three structurally related peptides: atrial natriuretic peptide, brain natriuretic peptide (BNP), and C-type natriuretic peptide. Atrial natriuretic peptide and BNP are cardiac hormones that are produced predominantly by the atrium and ventricle, respectively. C-type natriuretic peptide occurs in a wide variety of tissues, where it acts as a local regulator. These peptides can influence body fluid homeostasis and blood pressure control through the activation of two guanylyl cyclase (GC)-coupled natriuretic peptide receptor subtypes - GC-A and GC-B. We report here marked skeletal overgrowth in transgenic mice that overexpress BNP. Transgenic mice with elevated plasma BNP concentrations exhibited deformed bony skeletons characterized by kyphosis, elongated limbs and paws, and crooked tails, Bone abnormalities resulted from a high turnover of endochondral ossification accompanied by overgrowth of the growth plate. Studies using an in vitro organ culture of embryonic mouse tibias revealed that BNP increases the height of cartilaginous primordium directly, thereby stimulating the total longitudinal bone growth. The present study demonstrates that natriuretic peptides can affect the process of endochondral ossification.

Original languageEnglish
Pages (from-to)2337-2342
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number5
DOIs
Publication statusPublished - 1998 Mar 3
Externally publishedYes

Fingerprint

Brain Natriuretic Peptide
Natriuretic Peptides
Transgenic Mice
Osteogenesis
C-Type Natriuretic Peptide
Growth Plate
Guanylate Cyclase
Bone Development
Atrial Natriuretic Factor
Bone and Bones
Kyphosis
Peptides
Peptide Receptors
Organ Culture Techniques
Body Fluids
Tibia
Skeleton
Tail
Spine
Homeostasis

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Skeletal overgrowth in transgenic mice that overexpress brain natriuretic peptide. / Suda, Michio; Ogawa, Yoshihiro; Tanaka, Kiyoshi; Tamura, Naohisa; Yasoda, Akihiro; Takigawa, Toshiya; Uehira, Masahiro; Nishimoto, Hirofumi; Itoh, Hiroshi; Saito, Yoshihiko; Shiota, Kohei; Nakao, Kazuwa.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 95, No. 5, 03.03.1998, p. 2337-2342.

Research output: Contribution to journalArticle

Suda, M, Ogawa, Y, Tanaka, K, Tamura, N, Yasoda, A, Takigawa, T, Uehira, M, Nishimoto, H, Itoh, H, Saito, Y, Shiota, K & Nakao, K 1998, 'Skeletal overgrowth in transgenic mice that overexpress brain natriuretic peptide', Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 5, pp. 2337-2342. https://doi.org/10.1073/pnas.95.5.2337
Suda, Michio ; Ogawa, Yoshihiro ; Tanaka, Kiyoshi ; Tamura, Naohisa ; Yasoda, Akihiro ; Takigawa, Toshiya ; Uehira, Masahiro ; Nishimoto, Hirofumi ; Itoh, Hiroshi ; Saito, Yoshihiko ; Shiota, Kohei ; Nakao, Kazuwa. / Skeletal overgrowth in transgenic mice that overexpress brain natriuretic peptide. In: Proceedings of the National Academy of Sciences of the United States of America. 1998 ; Vol. 95, No. 5. pp. 2337-2342.
@article{86f57f4962b54e23865f3dbddfb0db0b,
title = "Skeletal overgrowth in transgenic mice that overexpress brain natriuretic peptide",
abstract = "Longitudinal bone growth is determined by the process of endochondral ossification in the cartilaginous growth plate, which is located at both ends of vertebrae and long bones and involves many systemic hormones and local regulators. Natriuretic peptides organize a family of three structurally related peptides: atrial natriuretic peptide, brain natriuretic peptide (BNP), and C-type natriuretic peptide. Atrial natriuretic peptide and BNP are cardiac hormones that are produced predominantly by the atrium and ventricle, respectively. C-type natriuretic peptide occurs in a wide variety of tissues, where it acts as a local regulator. These peptides can influence body fluid homeostasis and blood pressure control through the activation of two guanylyl cyclase (GC)-coupled natriuretic peptide receptor subtypes - GC-A and GC-B. We report here marked skeletal overgrowth in transgenic mice that overexpress BNP. Transgenic mice with elevated plasma BNP concentrations exhibited deformed bony skeletons characterized by kyphosis, elongated limbs and paws, and crooked tails, Bone abnormalities resulted from a high turnover of endochondral ossification accompanied by overgrowth of the growth plate. Studies using an in vitro organ culture of embryonic mouse tibias revealed that BNP increases the height of cartilaginous primordium directly, thereby stimulating the total longitudinal bone growth. The present study demonstrates that natriuretic peptides can affect the process of endochondral ossification.",
author = "Michio Suda and Yoshihiro Ogawa and Kiyoshi Tanaka and Naohisa Tamura and Akihiro Yasoda and Toshiya Takigawa and Masahiro Uehira and Hirofumi Nishimoto and Hiroshi Itoh and Yoshihiko Saito and Kohei Shiota and Kazuwa Nakao",
year = "1998",
month = "3",
day = "3",
doi = "10.1073/pnas.95.5.2337",
language = "English",
volume = "95",
pages = "2337--2342",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "5",

}

TY - JOUR

T1 - Skeletal overgrowth in transgenic mice that overexpress brain natriuretic peptide

AU - Suda, Michio

AU - Ogawa, Yoshihiro

AU - Tanaka, Kiyoshi

AU - Tamura, Naohisa

AU - Yasoda, Akihiro

AU - Takigawa, Toshiya

AU - Uehira, Masahiro

AU - Nishimoto, Hirofumi

AU - Itoh, Hiroshi

AU - Saito, Yoshihiko

AU - Shiota, Kohei

AU - Nakao, Kazuwa

PY - 1998/3/3

Y1 - 1998/3/3

N2 - Longitudinal bone growth is determined by the process of endochondral ossification in the cartilaginous growth plate, which is located at both ends of vertebrae and long bones and involves many systemic hormones and local regulators. Natriuretic peptides organize a family of three structurally related peptides: atrial natriuretic peptide, brain natriuretic peptide (BNP), and C-type natriuretic peptide. Atrial natriuretic peptide and BNP are cardiac hormones that are produced predominantly by the atrium and ventricle, respectively. C-type natriuretic peptide occurs in a wide variety of tissues, where it acts as a local regulator. These peptides can influence body fluid homeostasis and blood pressure control through the activation of two guanylyl cyclase (GC)-coupled natriuretic peptide receptor subtypes - GC-A and GC-B. We report here marked skeletal overgrowth in transgenic mice that overexpress BNP. Transgenic mice with elevated plasma BNP concentrations exhibited deformed bony skeletons characterized by kyphosis, elongated limbs and paws, and crooked tails, Bone abnormalities resulted from a high turnover of endochondral ossification accompanied by overgrowth of the growth plate. Studies using an in vitro organ culture of embryonic mouse tibias revealed that BNP increases the height of cartilaginous primordium directly, thereby stimulating the total longitudinal bone growth. The present study demonstrates that natriuretic peptides can affect the process of endochondral ossification.

AB - Longitudinal bone growth is determined by the process of endochondral ossification in the cartilaginous growth plate, which is located at both ends of vertebrae and long bones and involves many systemic hormones and local regulators. Natriuretic peptides organize a family of three structurally related peptides: atrial natriuretic peptide, brain natriuretic peptide (BNP), and C-type natriuretic peptide. Atrial natriuretic peptide and BNP are cardiac hormones that are produced predominantly by the atrium and ventricle, respectively. C-type natriuretic peptide occurs in a wide variety of tissues, where it acts as a local regulator. These peptides can influence body fluid homeostasis and blood pressure control through the activation of two guanylyl cyclase (GC)-coupled natriuretic peptide receptor subtypes - GC-A and GC-B. We report here marked skeletal overgrowth in transgenic mice that overexpress BNP. Transgenic mice with elevated plasma BNP concentrations exhibited deformed bony skeletons characterized by kyphosis, elongated limbs and paws, and crooked tails, Bone abnormalities resulted from a high turnover of endochondral ossification accompanied by overgrowth of the growth plate. Studies using an in vitro organ culture of embryonic mouse tibias revealed that BNP increases the height of cartilaginous primordium directly, thereby stimulating the total longitudinal bone growth. The present study demonstrates that natriuretic peptides can affect the process of endochondral ossification.

UR - http://www.scopus.com/inward/record.url?scp=13144277562&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=13144277562&partnerID=8YFLogxK

U2 - 10.1073/pnas.95.5.2337

DO - 10.1073/pnas.95.5.2337

M3 - Article

C2 - 9482886

AN - SCOPUS:13144277562

VL - 95

SP - 2337

EP - 2342

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 5

ER -