Figure 5.

Bone-Targeting AAV9-Mediated Silencing of ctsk Reverses Bone Loss in a Mouse Model of Postmenopausal Osteoporosis

(A) Timeline of the study and treatment methods. (B–J) Sham or OVX surgery was performed on 3-month-old female mice. Six weeks later, a single dose of 8 × 10¹¹ GC of rAAV9.DSS-Nter carrying amiR-ctrl or amiR-ctsk was i.v. injected. (B) Seven weeks after injection, ctsk mRNA levels were assessed in the tibia (B, n = 8/group). Femoral trabecular bone mass was assessed by microCT. (C and D) Representative 3D reconstruction (D) and relative quantifications (C) are displayed (n = 8/group). (E–H) Histomorphometric quantification of ES/BS, N.OC/T.Ar (E), representative calcein/alizarin red labeling (F), BFR/BS, MAR (G), and OB.S/BS (H) are displayed (n = 8–9/group). (I) sphk1 mRNA levels in the tibia were assessed by RT-PCR and normalized to hprt (n = 8). (J) Femoral biomechanical properties, including bending rigidity and moment, apparent bending stress, and work to bending moment were quantified (n = 7/group). Values represent mean ± SD. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001 by an unpaired two-tailed Student’s t test and one-way ANOVA test. N.S., not significant.