Fig. 2.
PTH1R ligand bias in vitro. A. Multiaxial plot of PTH analog efficacy in cAMP, calcium and ERK1/2 assays performed using HEK293 cells overexpressing human PTH1R. Estimated RAi values for each ligand are plotted to represent the magnitude and direction of effect in each signaling response. Figure adapted from Appleton et al. (2013) Methods Enzymol 522: 229–262 [52]. B. Effects of hPTH(1–34) and [D-Trp12,Tyr34]-bPTH(7–34) [bPTH(7–34)] on cAMP production (left) and ERK1/2 activation (right) in 10 day-old cultures of differentiating primary calvarial osteoblasts isolated from wild type (WT) and β-arrestin2−/− mice. Figure adapted from Gesty-Palmer et al. (2009) Science – Transl Med 1ra1 [33]. C. Effects of hPTH (1–34) and [D-Trp12,Tyr34]-bPTH(7–34) on the survival and random migration of primary calvarial osteoblasts isolated from wild type and β-arrestin2−/− mice. Anti-apoptotic effects (left) were measured in 10 day-old differentiating osteoblast cultures subjected to serum-withdrawal or exposed to etoposide in the presence or absence of hPTH(1–34) or [D-Trp12,Tyr34]-bPTH(7–34). Random cell migration (right) was measured by scratch assay performed on 3-day old confluent monolayers of primary preosteoblasts. Figure adapted from Gesty-Palmer et al. Mol Endocrinol 27:296–314 [55].