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. 2019 Jan 8;7:2. doi: 10.1038/s41413-018-0038-3

Fig. 3.

Fig. 3

NOTUM inhibition increases endocortical bone formation. af Treatment with NOTUM inhibitor LP-922056. ab Male mice were given LP-922056 (10 mg·kg−1 per day) by diet administration for 4 weeks. Serum levels of type 1 procollagen N-terminal propeptide (a, P1NP, N = 24) and alkaline phosphatase (b, ALP, N: control = 19, LP-922056 = 21) on day 7. df Dynamic histomorphometry of midshaft femur cortical bone. 10-week-old male mice were treated twice weekly with LP-922056 (30 mg·kg−1) by oral gavage for 4 weeks. Mice were injected with demeclocycline, alizarin and calcein at days 3, 9 and 23, respectively (N: control = 16, LP-922056 = 12). c Single-labeled endocortical surface (Ec.sLS). d Endocortical mineralized surface per bone surface (Ec.MS/BS). e Endocortical mineral apposition rate (Ec.MAR). f Endocortical bone formation rate (Ec.BFR). g Female mice treated with LP-922056 by daily oral gavage for one week. mRNA levels of Alp, Sost and Ctsk in tibia shaft cortical bone from vehicle (control, N = 10) and LP-922056 (30 mg·kg−1; N = 9) mice. hj Female mice treated by daily oral gavage (control, N = 8) and LP-922056 (30 mg·kg−1; N = 8) for 4 weeks. h Serum levels of type I collagen C-terminal degradation fragments (CTX-I), i, j Static histomorphometry of osteoclasts in the midshaft femur. Osteoclast surface per bone surface (i, Oc.S/BS; control values were (2.3 ± 0.6)% and (23.7 ± 3.1)% for endocortical and periosteal surfaces, respectively) and number of osteoclasts per bone perimeter (j, N.Oc./B.Pm.; control values were (0.95 ± 0.21)  mm−1 and (7.94 ± 0.80)  mm−1 for endocortical and periosteal surfaces, respectively) expressed as % of control. kn Treatment with NOTUM inhibitor LP-914822 (N = 13). Male mice were given LP-914822 (30 mg·kg−1) by twice daily oral gavage for 25 days. The mice were injected with demeclocycline, alizarin and calcein at days 0, 6 and 16, respectively. k Single labeled periosteal surface (Ps.sLS), l Single labeled endocortical surface (Ec.sLS). m Endocortical mineral apposition rate for days 6 to 16 (Ec.MAR). n Endocortical and periosteal bone formation rates for days 6 to 16 (BFR). Values are means ± SEM. *P < 0.05 and **P < 0.01 vs control