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Publication : Sclerostin Antibody Administration Converts Bone Lining Cells Into Active Osteoblasts.

First Author  Kim SW Year  2017
Journal  J Bone Miner Res Volume  32
Issue  5 Pages  892-901
PubMed ID  27862326 Mgi Jnum  J:253166
Mgi Id  MGI:6108671 Doi  10.1002/jbmr.3038
Citation  Kim SW, et al. (2017) Sclerostin Antibody Administration Converts Bone Lining Cells Into Active Osteoblasts. J Bone Miner Res 32(5):892-901
abstractText  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. (c) 2016 American Society for Bone and Mineral Research.
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