Papers of particular interest, published recently, have been highlighted as: • Of importance, •• Of major importance

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22. Fan, Y., et al., Parathyroid hormone directs bone marrow mesenchymal cell fate. Cell Metab, 2017.

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25. Madisen L, et al. A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nat Neurosci. 2010;13(1):133–40.

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26. Maes C, et al. Osteoblast precursors, but not mature osteoblasts, move into developing and fractured bones along with invading blood vessels. Dev Cell. 2010;19(2):329–44.

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27. •• Kim SW, et al. Intermittent parathyroid hormone administration converts quiescent lining cells to active osteoblasts. J Bone Miner Res. 2012;27(10):2075–84.Here, lineage tracing was first used to demonstrate that lining cells derive from mature osteoblasts. Moreover, genetically labeled lining cells had the capacity to become osteoblasts after intermittent PTH treatment

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28. Miller PD, et al. Effect of abaloparatide vs placebo on new vertebral fractures in postmenopausal women with osteoporosis: a randomized clinical trial. JAMA. 2016;316(7):722–33.

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31. Brunkow ME, et al. Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. Am J Hum Genet. 2001;68(3):577–89.

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33. Estrada K, et al. Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. Nat Genet. 2012;44(5):491–501.

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36. Ke HZ, et al. Sclerostin and Dickkopf-1 as therapeutic targets in bone diseases. Endocr Rev. 2012;33(5):747–83.

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37. • Ominsky MS, et al. Tissue-level mechanisms responsible for the increase in bone formation and bone volume by sclerostin antibody. J Bone Miner Res. 2014;29(6):1424–30.Histomorphometry was used to demonstrate that sclerostin antibody treatment dramatically reduces quiescent bone surfaces. These findings set the stage for subsequent lineage tracing studies to ask whether sclerostin antibody might directly activate bone lining cells

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38. Ominsky MS, et al. Differential temporal effects of sclerostin antibody and parathyroid hormone on cancellous and cortical bone and quantitative differences in effects on the osteoblast lineage in young intact rats. Bone. 2015;81:380–91.

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39. •• Kim, S.W., et al., Sclerostin antibody administration converts bone lining cells into active osteoblasts. J Bone Miner Res, 2016.Lineage tracing was used to track endosteal and periosteal lining cell responses to sclerostin antibody. Like PTH, sclerostin antibody directly converts quiescent bone lining cells to active matrix-forming osteoblasts.

40. • Matic, I., et al., Quiescent bone lining cells are a major source of osteoblasts during adulthood. Stem Cells, 2016.Lineage tracing was used to demonstrate that lining cells can contribute to osteoblastogenesis in the setting of osteoblast ablation.

41. •• Zhang, J. and D.C. Link, Targeting of mesenchymal stromal cells by Cre-recombinase transgenes commonly used to target osteoblast lineage cells. J Bone Miner Res, 2016.An important study that clearly illustrates some major technical limitations associated with lineage tracing techniques. Specifically, “osteoblast-specific” Cre driver lines show robust activity in multiple non-osteoblastic cell types.

42. Taylor S, et al. Time-dependent cellular and transcriptional changes in the osteoblast lineage associated with sclerostin antibody treatment in ovariectomized rats. Bone. 2016;84:148–59.

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43. Ono N, Kronenberg HM. Bone repair and stem cells. Curr Opin Genet Dev. 2016;40:103–7.

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44. Visnjic D, et al. Conditional ablation of the osteoblast lineage in Col2.3deltatk transgenic mice. J Bone Miner Res. 2001;16(12):2222–31.

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45. Ozcivici E, et al. Mechanical signals as anabolic agents in bone. Nat Rev Rheumatol. 2010;6(1):50–9.

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46. Robling AG, et al. Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin. J Biol Chem. 2008;283(9):5866–75.

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47. Tu X, et al. Sost downregulation and local Wnt signaling are required for the osteogenic response to mechanical loading. Bone. 2012;50(1):209–17.

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48. Chow JW, et al. Mechanical loading stimulates bone formation by reactivation of bone lining cells in 13-week-old rats. J Bone Miner Res. 1998;13(11):1760–7.

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49. Mavrogenis AF, et al. Side effects of radiation in musculoskeletal oncology: clinical evaluation of radiation-induced fractures. Int J Immunopathol Pharmacol. 2011;24(1 Suppl 2):29–37.

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50. Dominici M, et al. Restoration and reversible expansion of the osteoblastic hematopoietic stem cell niche after marrow radioablation. Blood. 2009;114(11):2333–43.

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51. Turner RT, et al. Acute exposure to high dose gamma-radiation results in transient activation of bone lining cells. Bone. 2013;57(1):164–73.

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52. Power RA, et al. Basic fibroblast growth factor has rapid bone anabolic effects in ovariectomized rats. Osteoporos Int. 2004;15(9):716–23.

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