Time-dependent effects of Scl-Ab on rat vertebral cancellous bone osteoblast and osteoprogenitor populations and osteocyte signaling pathways. (A) Total number of BrdU-positive osteoblasts at day 9 and day 29, (B) total osteoblast number, (C) cancellous mineralizing surface, (D) total peritrabecular osteoprogenitor number, (E) total marrow osteoprogenitor number, and (F) heat map of activation status of signaling pathways related to mitogenesis and cell cycle progression in the osteocyte based on an upstream regulator analysis (red indicates activation and blue indicates inhibition) in aged ovariectomized rats administered Scl-Ab through day 183, followed by a treatment-free period through day 309, modified from Taylor et al. (Taylor et al., 2016). See Taylor et al. (Taylor et al., 2016) for additional experimental details. Values shown are mean ± standard deviation. *p ≤ 0.05, 2-way analysis of variance, t-test, or Sidak's multiple comparison test, compared with vehicle. **p ≤ 0.05, Scl-Ab day 9 vs day 29. BrdU = 5-bromo-2′-deoxyuridine; CDKN1A = cyclin-dependent kinase inhibitor 1A; CDKN2A = CDKN inhibitor 2A; D = day; E2F1 = E2F transcription factor 1; FOXM1 = Forkhead box protein M1; MS/BS = mineralizing surface per bone surface; MYC = v-myc avian myelocytomatosis viral oncogene homolog; MYCN = MYC neuroblastoma-derived homolog; RB1 = retinoblastoma protein 1; Scl-Ab = sclerostin antibody; TP53 = tumor protein p53.