Figure 6. Bmp2 acts downstream of intermittent parathyroid hormone treatment in the juvenile periosteum.
Intermittent PTH1-34 therapy does not rescue periosteal growth in juvenile Bmp2 Prx1-cKO mice. (a) Juvenile mice were given intermittent PTH1-34 therapy (100 mg/kg, subcutaneous) for 14 days. (b) Longitudinal sections of the femur stained with toluidine blue to visualize trabecular bone architecture. (c) Transverse sections of the radius and ulna stained with toluidine blue to visualize cortical bone architecture. (d–g) Bone mass analyzed in the femur by microcomputed tomography (microCT). (d) Trabecular bone at the distal metaphysis and (e) cortical bone at the mid-diaphysis of the femur visualized by 3D reconstructions. Images represent the group mean and are shown to scale. (f) Ratio of bone volume (BV) to trabecular volume (TV). (g) Total cross-sectional area at the mid-diaphysis. Quantitative microCT data presented as mean ±s.d. where *p<0.05 vs. matched genotype vehicle control and #p<0.05 vs. WT vehicle control (n = 4–5 per group). (h,i) Dynamic histomorphometry assessing bone formation rate as a function of bone surface (BFR/BS) at (h) endosteal versus (i) periosteal surfaces. (j,k) Dynamic histomorphometry assessing mineral apposition rate (MAR) at (j) endosteal versus (k) periosteal surfaces. Dynamic histomorphometry (n = 4–5 per group) presented as mean ±s.d. where *p<0.05. BFRPO P-value=0.0503) vs. matched genotype vehicle control and #p<0.05 vs. WT vehicle control. (l,m) Elisa analysis measuring circulating (l) serum phosphate and (m) serum calcium in juvenile mice treated with intermittent PTH1-34 presented as mean ±s.d. where *p<0.05 vs. vehicle-treated Bmp2F/F or **p<0.05 vehicle-treated Bmp2 Prx1-cKO littermates. (n) Transverse sections of the radius/ulna with immunostaining to visualize cells expressing the BMP target gene, ID3. Abbreviations: PO, periosteum; Ma, marrow. n ≥ 3 histological sections were examined from multiple mice per cohort.