Sclerostin Antibody Administration Converts Bone Lining Cells Into Active Osteoblasts. (30th January 2017)

• Record Type: Journal Article
• Authors: Kim, Sang Wan; Lu, Yanhui; Williams, Elizabeth A; Lai, Forest; Lee, Ji Yeon; Enishi, Tetsuya; Balani, Deepak H; Ominsky, Michael S; Ke, Hua Zhu; Kronenberg, Henry M; Wein, Marc N
• Is Part Of: Journal of bone and mineral research. Volume 32:Number 5(2017:May)
• Page Start: 892
• Page End: 901
• Publication Date: 2017-01-30
• Subjects: OSTEOBLASTS -- MOLECULAR PATHWAYS–REMODELING -- WNT/ß‐CATENIN/LRPS -- ANABOLICS -- PRECLINICAL STUDIES; Bones -- Metabolism -- Periodicals; Mineral metabolism -- Periodicals; 612.392
• DOI: 10.1002/jbmr.3038
• Languages: English
• ISSNs: 0884-0431

Abstract

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. Abstract : Sclerostin antibody rapidly increases osteoblast numbers, but the underlying cellular mechanisms responsible remain unknown. Kim et al. used two lineage tracing models to demonstrate the sclerostin antibody directly converts quiescent bone lining cells into active osteoblasts.