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Sclerostin Antibody Administration Converts Bone Lining Cells Into Active Osteoblasts.

Authors :
Kim SW
Lu Y
Williams EA
Lai F
Lee JY
Enishi T
Balani DH
Ominsky MS
Ke HZ
Kronenberg HM
Wein MN
Source :
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research [J Bone Miner Res] 2017 May; Vol. 32 (5), pp. 892-901. Date of Electronic Publication: 2017 Jan 30.
Publication Year :
2017

Abstract

Sclerostin antibody (Scl-Ab) increases osteoblast activity, in part through increasing modeling-based bone formation on previously quiescent surfaces. Histomorphometric studies have suggested that this might occur through conversion of bone lining cells into active osteoblasts. However, direct data demonstrating Scl-Ab-induced conversion of lining cells into active osteoblasts are lacking. Here, we used in vivo lineage tracing to determine if Scl-Ab promotes the conversion of lining cells into osteoblasts on periosteal and endocortical bone surfaces in mice. Two independent, tamoxifen-inducible lineage-tracing strategies were used to label mature osteoblasts and their progeny using the DMP1 and osteocalcin promoters. After a prolonged "chase" period, the majority of labeled cells on bone surfaces assumed a thin, quiescent morphology. Then, mice were treated with either vehicle or Scl-Ab (25 mg/kg) twice over the course of the subsequent week. After euthanization, marked cells were enumerated, their thickness quantified, and proliferation and apoptosis examined. Scl-Ab led to a significant increase in the average thickness of labeled cells on periosteal and endocortical bone surfaces, consistent with osteoblast activation. Scl-Ab did not induce proliferation of labeled cells, and Scl-Ab did not regulate apoptosis of labeled cells. Therefore, direct reactivation of quiescent bone lining cells contributes to the acute increase in osteoblast numbers after Scl-Ab treatment in mice. © 2016 American Society for Bone and Mineral Research.<br /> (© 2016 American Society for Bone and Mineral Research.)

Details

Language :
English
ISSN :
1523-4681
Volume :
32
Issue :
5
Database :
MEDLINE
Journal :
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
Publication Type :
Academic Journal
Accession number :
27862326
Full Text :
https://doi.org/10.1002/jbmr.3038