Sclerostin is expressed in osteoclasts from aged mice and reduces osteoclast-mediated stimulation of mineralization

Kuniaki Ota, Patrick Quint, Ming Ruan, Larry Pederson, Jennifer J Westendorf, Sundeep Khosla, Merry Jo Oursler

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Osteoclast-mediated bone resorption precedes osteoblast-mediated bone formation through early adulthood, but formation fails to keep pace with resorption during aging. We previously identified several factors produced by osteoclasts that promote bone formation. In this study, we determined if osteoclast-produced factors contribute to the impaired bone formation with aging. We previously found that mice between the ages of 18 and 22 months develop age-related bone loss. Bone marrow-derived pre-osteoclasts were isolated from 6-week, 12-month, and 18- to 24-month-old mice and differentiated into osteoclasts in vitro. Conditioned media were collected and compared for osteoblast mineralization support. Conditioned medium from osteoclasts from all ages was able to support mineralization of bone marrow stromal cells. Concentrating the conditioned medium from 6-week-old and 12-month-old mouse marrow cells-derived osteoclasts enhanced mineralization support whereas concentrated conditioned medium from 18- to 24-month-old mouse marrow-derived osteoclasts repressed mineralization compared to base medium. This observation suggests that an inhibitor of mineralization was secreted by aged murine osteoclasts. Gene and protein analysis revealed that the Wnt antagonist sclerostin was significantly elevated in the conditioned media from 24-month-old mouse cells compared to 6-week-old mouse cells. Antibodies directed to sclerostin neutralized the influences of the aged mouse cell concentrated conditioned media on mineralization. Sclerostin is primarily produced by osteocytes in young animals. This study demonstrates that osteoclasts from aged mice also produce sclerostin in quantities that may contribute to the age-related impairment in bone formation.

Original languageEnglish (US)
Pages (from-to)1901-1907
Number of pages7
JournalJournal of Cellular Biochemistry
Volume114
Issue number8
DOIs
StatePublished - Aug 2013

Fingerprint

Osteoclasts
Bone
Conditioned Culture Medium
Osteogenesis
Bone Marrow
Osteoblasts
Aging of materials
Osteocytes
Bone Resorption
Mesenchymal Stromal Cells
Osteoporosis
Animals
Cells
Antibodies

Keywords

  • AGING
  • OSTEOCLAST
  • SCLEROSTIN

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Sclerostin is expressed in osteoclasts from aged mice and reduces osteoclast-mediated stimulation of mineralization. / Ota, Kuniaki; Quint, Patrick; Ruan, Ming; Pederson, Larry; Westendorf, Jennifer J; Khosla, Sundeep; Oursler, Merry Jo.

In: Journal of Cellular Biochemistry, Vol. 114, No. 8, 08.2013, p. 1901-1907.

Research output: Contribution to journalArticle

@article{eaf1d26e8b2445f887418e7e1e8360bd,
title = "Sclerostin is expressed in osteoclasts from aged mice and reduces osteoclast-mediated stimulation of mineralization",
abstract = "Osteoclast-mediated bone resorption precedes osteoblast-mediated bone formation through early adulthood, but formation fails to keep pace with resorption during aging. We previously identified several factors produced by osteoclasts that promote bone formation. In this study, we determined if osteoclast-produced factors contribute to the impaired bone formation with aging. We previously found that mice between the ages of 18 and 22 months develop age-related bone loss. Bone marrow-derived pre-osteoclasts were isolated from 6-week, 12-month, and 18- to 24-month-old mice and differentiated into osteoclasts in vitro. Conditioned media were collected and compared for osteoblast mineralization support. Conditioned medium from osteoclasts from all ages was able to support mineralization of bone marrow stromal cells. Concentrating the conditioned medium from 6-week-old and 12-month-old mouse marrow cells-derived osteoclasts enhanced mineralization support whereas concentrated conditioned medium from 18- to 24-month-old mouse marrow-derived osteoclasts repressed mineralization compared to base medium. This observation suggests that an inhibitor of mineralization was secreted by aged murine osteoclasts. Gene and protein analysis revealed that the Wnt antagonist sclerostin was significantly elevated in the conditioned media from 24-month-old mouse cells compared to 6-week-old mouse cells. Antibodies directed to sclerostin neutralized the influences of the aged mouse cell concentrated conditioned media on mineralization. Sclerostin is primarily produced by osteocytes in young animals. This study demonstrates that osteoclasts from aged mice also produce sclerostin in quantities that may contribute to the age-related impairment in bone formation.",
keywords = "AGING, OSTEOCLAST, SCLEROSTIN",
author = "Kuniaki Ota and Patrick Quint and Ming Ruan and Larry Pederson and Westendorf, {Jennifer J} and Sundeep Khosla and Oursler, {Merry Jo}",
year = "2013",
month = "8",
doi = "10.1002/jcb.24537",
language = "English (US)",
volume = "114",
pages = "1901--1907",
journal = "Journal of Cellular Biochemistry",
issn = "0730-2312",
publisher = "Wiley-Liss Inc.",
number = "8",

}

TY - JOUR

T1 - Sclerostin is expressed in osteoclasts from aged mice and reduces osteoclast-mediated stimulation of mineralization

AU - Ota, Kuniaki

AU - Quint, Patrick

AU - Ruan, Ming

AU - Pederson, Larry

AU - Westendorf, Jennifer J

AU - Khosla, Sundeep

AU - Oursler, Merry Jo

PY - 2013/8

Y1 - 2013/8

N2 - Osteoclast-mediated bone resorption precedes osteoblast-mediated bone formation through early adulthood, but formation fails to keep pace with resorption during aging. We previously identified several factors produced by osteoclasts that promote bone formation. In this study, we determined if osteoclast-produced factors contribute to the impaired bone formation with aging. We previously found that mice between the ages of 18 and 22 months develop age-related bone loss. Bone marrow-derived pre-osteoclasts were isolated from 6-week, 12-month, and 18- to 24-month-old mice and differentiated into osteoclasts in vitro. Conditioned media were collected and compared for osteoblast mineralization support. Conditioned medium from osteoclasts from all ages was able to support mineralization of bone marrow stromal cells. Concentrating the conditioned medium from 6-week-old and 12-month-old mouse marrow cells-derived osteoclasts enhanced mineralization support whereas concentrated conditioned medium from 18- to 24-month-old mouse marrow-derived osteoclasts repressed mineralization compared to base medium. This observation suggests that an inhibitor of mineralization was secreted by aged murine osteoclasts. Gene and protein analysis revealed that the Wnt antagonist sclerostin was significantly elevated in the conditioned media from 24-month-old mouse cells compared to 6-week-old mouse cells. Antibodies directed to sclerostin neutralized the influences of the aged mouse cell concentrated conditioned media on mineralization. Sclerostin is primarily produced by osteocytes in young animals. This study demonstrates that osteoclasts from aged mice also produce sclerostin in quantities that may contribute to the age-related impairment in bone formation.

AB - Osteoclast-mediated bone resorption precedes osteoblast-mediated bone formation through early adulthood, but formation fails to keep pace with resorption during aging. We previously identified several factors produced by osteoclasts that promote bone formation. In this study, we determined if osteoclast-produced factors contribute to the impaired bone formation with aging. We previously found that mice between the ages of 18 and 22 months develop age-related bone loss. Bone marrow-derived pre-osteoclasts were isolated from 6-week, 12-month, and 18- to 24-month-old mice and differentiated into osteoclasts in vitro. Conditioned media were collected and compared for osteoblast mineralization support. Conditioned medium from osteoclasts from all ages was able to support mineralization of bone marrow stromal cells. Concentrating the conditioned medium from 6-week-old and 12-month-old mouse marrow cells-derived osteoclasts enhanced mineralization support whereas concentrated conditioned medium from 18- to 24-month-old mouse marrow-derived osteoclasts repressed mineralization compared to base medium. This observation suggests that an inhibitor of mineralization was secreted by aged murine osteoclasts. Gene and protein analysis revealed that the Wnt antagonist sclerostin was significantly elevated in the conditioned media from 24-month-old mouse cells compared to 6-week-old mouse cells. Antibodies directed to sclerostin neutralized the influences of the aged mouse cell concentrated conditioned media on mineralization. Sclerostin is primarily produced by osteocytes in young animals. This study demonstrates that osteoclasts from aged mice also produce sclerostin in quantities that may contribute to the age-related impairment in bone formation.

KW - AGING

KW - OSTEOCLAST

KW - SCLEROSTIN

UR - http://www.scopus.com/inward/record.url?scp=84879159387&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84879159387&partnerID=8YFLogxK

U2 - 10.1002/jcb.24537

DO - 10.1002/jcb.24537

M3 - Article

C2 - 23494985

AN - SCOPUS:84879159387

VL - 114

SP - 1901

EP - 1907

JO - Journal of Cellular Biochemistry

JF - Journal of Cellular Biochemistry

SN - 0730-2312

IS - 8

ER -