Loss of adipogenic dickkopf-1 increases trabecular and cortical bone mass by promoting bone formation in male mice

Intermittent PTH treatment increases cancellous bone mass in osteoporosis patients; however, it reveals diverse effects on cortical bone mass. Underlying molecular mechanisms for anabolic PTH actions are largely unknown. Because PTH regulates expression of osteopontin (OPN) in osteoblasts, OPN could be one of the targets of PTH in bone. Therefore, we examined the role of OPN in the PTH actions in bone. Intermittent PTH treatment neither altered whole long-bone bone mineral density nor changed cortical bone mass in wild-type 129 mice, although it enhanced cancellous bone volume as reported previously. In contrast, OPN deficiency induced PTH enhancement of whole-bone bone mineral density as well as cortical bone mass. Strikingly, although PTH suppressed periosteal bone formation rate (BFR) and mineral apposition rate (MAR) in cortical bone in wild type, OPN deficiency induced PTH activation of periosteal BFR and MAR. In cancellous bone, OPN deficiency further enhanced PTH increase in BFR and MAR. Analysis on the cellular bases for these phenomena indicated that OPN deficiency augmented PTH enhancement in the increase in mineralized nodule formation in vitro. OPN deficiency did not alter the levels of PTH enhancement of the excretion of deoxypyridinoline in urine, the osteoclast number in vivo, and tartrate-resistant acid phosphatase-positive cell development in vitro. These observations indicated that OPN deficiency specifically induces PTH activation of periosteal bone formation in the cortical bone envelope.

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A New Synthetic Steroid, Osaterone Acetate (TZP-4238), Increases Cortical Bone Mass and Strength by Enhancing Bone Formation in Ovariectomized Rats

Journal of Bone and Mineral Research ◽

10.1359/jbmr.1997.12.4.590 ◽

1997 ◽

Vol 12 (4) ◽

pp. 590-597 ◽

Cited By ~ 13

Author(s):

Hiroaki Fuse ◽

Seiji Fukumoto ◽

Hideyuki Sone ◽

Yoshiko Miyata ◽

Tomoyuki Saito ◽

...

Keyword(s):

Bone Formation ◽

Bone Mass ◽

Cortical Bone ◽

Ovariectomized Rats ◽

Cortical Bone Mass

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Cortical bone adaptation to a moderate level of mechanical loading in male Sost deficient mice

Scientific Reports ◽

10.1038/s41598-020-79098-0 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Haisheng Yang ◽

Alexander Büttner ◽

Laia Albiol ◽

Catherine Julien ◽

Tobias Thiele ◽

...

Keyword(s):

Physical Activity ◽

Bone Formation ◽

Bone Mass ◽

Cortical Bone ◽

Bone Adaptation ◽

Moderate Level ◽

Skeletal Maturation ◽

Male Mice ◽

Males And Females

AbstractLoss-of-function mutations in the Sost gene lead to high bone mass phenotypes. Pharmacological inhibition of Sost/sclerostin provides a new drug strategy for treating osteoporosis. Questions remain as to how physical activity may affect bone mass under sclerostin inhibition and if that effect differs between males and females. We previously observed in female Sost knockout (KO) mice an enhanced cortical bone formation response to a moderate level of applied loading (900 με at the tibial midshaft). The purpose of the present study was to examine cortical bone adaptation to the same strain level applied to male Sost KO mice. Strain-matched in vivo compressive loading was applied to the tibiae of 10-, 26- and 52-week-old male Sost KO and littermate control (LC) mice. The effect of tibial loading on bone (re)modeling was measured by microCT, 3D time-lapse in vivo morphometry, 2D histomorphometry and gene expression analyses. As expected, Sost deficiency led to high cortical bone mass in 10- and 26-week-old male mice as a result of increased bone formation. However, the enhanced bone formation associated with Sost deficiency did not appear to diminish with skeletal maturation. An increase in bone resorption was observed with skeletal maturation in male LC and Sost KO mice. Two weeks of in vivo loading (900 με at the tibial midshaft) induced only a mild anabolic response in 10- and 26-week-old male mice, independent of Sost deficiency. A decrease in the Wnt inhibitor Dkk1 expression was observed 3 h after loading in 52-week-old Sost KO and LC mice, and an increase in Lef1 expression was observed 8 h after loading in 10-week-old Sost KO mice. The current results suggest that long-term inhibition of sclerostin in male mice does not influence the adaptive response of cortical bone to moderate levels of loading. In contrast with our previous strain-matched study in females showing enhanced bone responses with Sost ablation, these results in males indicate that the influence of Sost deficiency on the cortical bone formation response to a moderate level of loading differs between males and females. Clinical studies examining antibodies to inhibit sclerostin may need to consider that the efficacy of additional physical activity regimens may be sex dependent.

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Metformin Affects Cortical Bone Mass and Marrow Adiposity in Diet-Induced Obesity in Male Mice

Endocrinology ◽

10.1210/en.2017-00299 ◽

2017 ◽

Vol 158 (10) ◽

pp. 3369-3385 ◽

Cited By ~ 22

Author(s):

Sheila Bornstein ◽

Michele Moschetta ◽

Yawara Kawano ◽

Antonio Sacco ◽

Daisy Huynh ◽

...

Keyword(s):

Bone Mass ◽

Cortical Bone ◽

Male Mice ◽

Diet Induced Obesity ◽

Marrow Adiposity ◽

Cortical Bone Mass

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Exercise enhanced tibial cortical bone mass by stimulated periosteal bone formation and surpressed endosteal bone resorption in female adult aged rats

Bone ◽

10.1016/8756-3282(92)90482-c ◽

1992 ◽

Vol 13 (5) ◽

pp. A7-A7

Author(s):

M.M. Chen ◽

J.K. Yen ◽

J.F. Aloia ◽

J.M. Tierney

Keyword(s):

Bone Resorption ◽

Bone Formation ◽

Bone Mass ◽

Cortical Bone ◽

Aged Rats ◽

Female Adult ◽

Periosteal Bone Formation ◽

Cortical Bone Mass ◽

Tibial Cortical Bone

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IL-23 receptor deficiency results in lower bone mass via indirect regulation of bone formation

Scientific Reports ◽

10.1038/s41598-021-89625-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Wida Razawy ◽

Celso H. Alves ◽

Marijke Koedam ◽

Patrick S. Asmawidjaja ◽

Adriana M. C. Mus ◽

...

Keyword(s):

Bone Formation ◽

Bone Mass ◽

Cortical Bone ◽

Bone Growth ◽

Osteoclast Differentiation ◽

Bone Homeostasis ◽

Littermate Control ◽

Cortical Bone Mass

AbstractThe IL-23 receptor (IL-23R) signaling pathway has pleiotropic effects on the differentiation of osteoclasts and osteoblasts, since it can inhibit or stimulate these processes via different pathways. However, the potential role of this pathway in the regulation of bone homeostasis remains elusive. Therefore, we studied the role of IL-23R signaling in physiological bone remodeling using IL-23R deficient mice. Using µCT, we demonstrate that 7-week-old IL-23R−/− mice have similar bone mass as age matched littermate control mice. In contrast, 12-week-old IL-23R−/− mice have significantly lower trabecular and cortical bone mass, shorter femurs and more fragile bones. At the age of 26 weeks, there were no differences in trabecular bone mass and femur length, but most of cortical bone mass parameters remain significantly lower in IL-23R−/− mice. In vitro osteoclast differentiation and resorption capacity of 7- and 12-week-old IL-23R−/− mice are similar to WT. However, serum levels of the bone formation marker, PINP, are significantly lower in 12-week-old IL-23R−/− mice, but similar to WT at 7 and 26 weeks. Interestingly, Il23r gene expression was not detected in in vitro cultured osteoblasts, suggesting an indirect effect of IL-23R. In conclusion, IL-23R deficiency results in temporal and long-term changes in bone growth via regulation of bone formation.

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Blocking Oxidized Phospholipids Attenuates the Age-Associated, but Not the Ovariectomy- or Unloading- Induced, Bone Loss in Mice

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.470 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A231-A232

Author(s):

Michela Palmieri ◽

Teenamol E Joseph ◽

Aaron Warren ◽

Horacio Gomez-acevedo ◽

Jinhu Xiong ◽

...

Keyword(s):

Bone Loss ◽

Transgenic Mice ◽

Bone Mass ◽

Cortical Bone ◽

Micro Ct ◽

Oxidized Phospholipids ◽

Male Mice ◽

Male And Female ◽

Age Related ◽

Cortical Bone Mass

Abstract Oxidized phospholipids (OxPL), such as oxidized phosphatidylcholine, are generated by oxidative stress (OS)-induced lipid peroxidation. E06 IgM is a natural antibody that recognizes the phosphocholine (PC) moiety of OxPLs, but not native PLs. Generation of transgenic mice expressing a single chain (scFv) form of its antigen-binding domain, “E06-scFv” mice, protects against atherosclerosis, hepatic steatosis and high fat diet-induced loss of bone mass. In addition, E06-scFv increases cancellous and cortical bone mass in both male and female adult mice fed chow diet, by increasing bone formation. Age-related bone loss is associated with increased OS and lipid peroxidation, and is characterized by a reduction in osteoblast number and bone formation. Oxidative stress is involved also in the bone loss caused by sex-steroid deficiency and elevated OS markers are found in unloading-induced bone loss, raising the possibility that an increase of OxPLs induced by OS might be contributing to the pathogenesis of these conditions as well. We aged homozygous E06-scFv transgenic female and male mice and their wild-type littermates up to 22 and 24 months respectively. Serial DXA BMD every 3 months showed that overexpression of E06-scFv attenuated the age-associated bone loss in both sexes. In addition, male and female E06-scFv transgenic mice also accumulated less fat mass than WT littermates during aging. Micro-CT analysis revealed that E06-scFv attenuated the age-associated decline in cancellous, but not cortical, bone mass. The histological analysis of the vertebrae indicated that the aged E06-scFv transgenic mice had increased osteoblasts and decreased osteoclasts compared to the WT mice. To investigate whether the beneficial effect of the E06-scFv could be seen after ovariectomy, 4.5 month old E06-scFv homozygous females and WT controls were ovariectomized (OVX). DXA and micro-CT measurements 6 weeks post- surgery indicated that, unlike aging, E06-scFv did not protect against OVX-induced bone loss in either the cancellous or the cortical compartment. Lastly, we tail-suspended 5.5 month old male mice and sacrificed them 21 days later. E06-scFv transgenic mice had similar cortical bone loss compared to WT mice. In conclusion, the E06-scFV transgene attenuates the age-associated cancellous bone loss in both female and male mice, but has no effect on the OVX- or unloading-induced bone loss. These results fully support our hypothesis that an increase in PC-OxPLs with age, caused at least in part by a decrease in natural anti-PC antibodies, contributes to the age-associated bone loss. This evidence provides proof of concept that blocking PC-OxPLs represents a therapeutic approach to countering the increase of PC-OxPLs with age and their adverse effects on age-related bone loss as well as atherosclerosis and NASH. It also confirms that the mechanisms of cancellous and cortical bone loss are distinct.

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Influence of Gastrectomy on Cortical and Cancellous Bones in Rats

Gastroenterology Research and Practice ◽

10.1155/2013/381616 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 6

Author(s):

Jun Iwamoto ◽

Yoshihiro Sato ◽

Hideo Matsumoto

Keyword(s):

Bone Formation ◽

Bone Mass ◽

Cortical Bone ◽

Cancellous Bone ◽

Femoral Diaphysis ◽

Control Group ◽

Sham Operation ◽

Sprague Dawley ◽

Osteoid Surface ◽

Cortical Bone Mass

The aim of the present study was to examine the influence of gastrectomy (GX) on cortical and cancellous bones in rats. Twenty male Sprague-Dawley rats were randomized into the two groups of 10 animals each: a sham operation (control) group and a GX group. Seven weeks after surgery, the bone mineral content and density (BMC and BMD, resp.) and the mechanical strength of the femur were determined, and bone histomorphometric analyses were performed on the tibia. GX induced decreases in the BMC, BMD, ultimate force, work to failure, and stiffness of the femoral distal metaphysis and the BMC, BMD, and ultimate force of the femoral diaphysis. GX induced a decrease in cancellous bone mass, characterized by an increased osteoid thickness, osteoid surface, osteoid volume, and bone formation. GX also induced a decrease in cortical bone mass, characterized by increased endocortical bone resorption. The GX induced reductions in the bone mass and strength parameters were greater in cancellous bone than in cortical bone. The present study showed that the response of bone formation, resorption, and osteoid parameters to GX and the degree of GX-induced osteopenia and the deterioration of bone strength appeared to differ between cortical and cancellous bones in rats.

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