THU0079 Anti-IL-6 Receptor Antibody Suppresses Systemic Bone Loss by not Only Normalizing Bone Resorption but also Enhancing Bone Formation in a Mouse Model of Collagen-Induced Arthritis

Osteoporosis and periodontal disease (PD) are two chronic diseases, characterized by bone loss, with systemic or local impact (alveolar bone). Both pathologies have a progressive evolution, leading to systemic bone loss in the case of osteoporosis and bone lysis localized in the alveolar bone in the case of periodontal disease. The present paper presents recent data from the literature on the association between periodontal disease and osteoporosis, on the role of cytokines in the bone resorption-apposition imbalance, and on how periodontal disease causes changes in serum levels of cytokines, leading to disorders in the systemic bone formation. We also found it useful, especially for rheumatologists, to outline the extent to which periodontal disease can create a systemic context favorable to the development of osteoporosis.

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An Uncoupling Agent Containing Strontium Prevents Bone Loss by Depressing Bone Resorption and Maintaining Bone Formation in Estrogen-Deficient Rats

Journal of Bone and Mineral Research ◽

10.1359/jbmr.2005.20.6.1065 ◽

2005 ◽

Vol 20 (6) ◽

pp. 1065-1074 ◽

Cited By ~ 10

Author(s):

Pierre J. Marie ◽

Monique Hott ◽

Dominique Modrowski ◽

Cinderella de Pollak ◽

Joel Guillemain ◽

...

Keyword(s):

Bone Resorption ◽

Bone Loss ◽

Bone Formation

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Novel Osteogenic Factors derived from Functional Food: Role in Prevention of Osteoporosis

Journal of Bone Biology and Osteoporosis ◽

10.18314/jbo.v1i1.9 ◽

2015 ◽

Vol 1 (1) ◽

Author(s):

Masayoshi Yamaguchi

Keyword(s):

Bone Resorption ◽

Bone Loss ◽

Bone Formation ◽

Functional Food ◽

Human Subjects ◽

Osteoclastic Bone Resorption ◽

Bone Homeostasis ◽

Osteoblastic Bone Formation ◽

Prevention Of Osteoporosis ◽

Osteogenic Effect

<p>Bone homeostasis is maintained through a delicate balance between osteoblastic bone formation and osteoclastic bone resorption. Bone loss is caused by decreasing in osteoblastic bone formation and increase in osteoclastic bone resorption, thereby leading to osteoporosis. Functional food factors may play a role in<br />the prevention of osteoporosis. Functional food factors including genistein, menaquinone-7 (vitamin K2) and β-cryptoxanthine have been shown to possess a potential osteogenic effect. These factors have been shown to reveal stimulatory effects on osteoblastic bone formation and suppressive effects on osteoclastic<br />bone resorption. Dietary intake of these factors has been shown to reveal preventive effects on bone loss in animal models of osteoporosis and human subjects. This review will introduce our findings concerning roles of functional food factors in regulation of bone homeostasis and prevention of osteoporosis.</p>

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Free Fatty Acid Receptor 4 (GPR120) Stimulates Bone Formation and Suppresses Bone Resorption in the Presence of Elevated n-3 Fatty Acid Levels

Endocrinology ◽

10.1210/en.2015-1855 ◽

2016 ◽

Vol 157 (7) ◽

pp. 2621-2635 ◽

Cited By ~ 23

Author(s):

Seong Hee Ahn ◽

Sook-Young Park ◽

Ji-Eun Baek ◽

Su-Youn Lee ◽

Wook-Young Baek ◽

...

Keyword(s):

Fatty Acid ◽

Free Fatty Acid ◽

Bone Resorption ◽

Bone Loss ◽

Bone Formation ◽

High Fat Diet ◽

Wild Type ◽

High Fat ◽

Free Fatty Acid Receptor

Free fatty acid receptor 4 (FFA4) has been reported to be a receptor for n-3 fatty acids (FAs). Although n-3 FAs are beneficial for bone health, a role of FFA4 in bone metabolism has been rarely investigated. We noted that FFA4 was more abundantly expressed in both mature osteoclasts and osteoblasts than their respective precursors and that it was activated by docosahexaenoic acid. FFA4 knockout (Ffar4−/−) and wild-type mice exhibited similar bone masses when fed a normal diet. Because fat-1 transgenic (fat-1Tg+) mice endogenously converting n-6 to n-3 FAs contain high n-3 FA levels, we crossed Ffar4−/− and fat-1Tg+ mice over two generations to generate four genotypes of mice littermates: Ffar4+/+;fat-1Tg−, Ffar4+/+;fat-1Tg+, Ffar4−/−;fat-1Tg−, and Ffar4−/−;fat-1Tg+. Female and male littermates were included in ovariectomy- and high-fat diet-induced bone loss models, respectively. Female fat-1Tg+ mice decreased bone loss after ovariectomy both by promoting osteoblastic bone formation and inhibiting osteoclastic bone resorption than their wild-type littermates, only when they had the Ffar4+/+ background, but not the Ffar4−/− background. In a high-fat diet-fed model, male fat-1Tg+ mice had higher bone mass resulting from stimulated bone formation and reduced bone resorption than their wild-type littermates, only when they had the Ffar4+/+ background, but not the Ffar4−/− background. In vitro studies supported the role of FFA4 as n-3 FA receptor in bone metabolism. In conclusion, FFA4 is a dual-acting factor that increases osteoblastic bone formation and decreases osteoclastic bone resorption, suggesting that it may be an ideal target for modulating metabolic bone diseases.

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Adrenomedullin22-52combats inflammation and prevents systemic bone loss in murine collagen-induced arthritis

Arthritis & Rheumatism ◽

10.1002/art.33426 ◽

2012 ◽

Vol 64 (4) ◽

pp. 1069-1081 ◽

Cited By ~ 8

Author(s):

Marie-Dominique Ah Kioon ◽

Carine Asensio ◽

Hang-Korng Ea ◽

Frédéric Velard ◽

Benjamin Uzan ◽

...

Keyword(s):

Bone Loss ◽

Collagen Induced Arthritis ◽

Systemic Bone Loss

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Porcupine inhibitors impair trabecular and cortical bone mass and strength in mice

Journal of Endocrinology ◽

10.1530/joe-18-0153 ◽

2018 ◽

Vol 238 (1) ◽

pp. 13-23 ◽

Cited By ~ 12

Author(s):

Thomas Funck-Brentano ◽

Karin H Nilsson ◽

Robert Brommage ◽

Petra Henning ◽

Ulf H Lerner ◽

...

Keyword(s):

Bone Resorption ◽

Bone Loss ◽

Bone Formation ◽

Bone Mass ◽

Trabecular Bone ◽

Cortical Bone ◽

Bone Strength ◽

Bending Test ◽

Bone Homeostasis ◽

Mineral Density

WNT signaling is involved in the tumorigenesis of various cancers and regulates bone homeostasis. Palmitoleoylation of WNTs by Porcupine is required for WNT activity. Porcupine inhibitors are under development for cancer therapy. As the possible side effects of Porcupine inhibitors on bone health are unknown, we determined their effects on bone mass and strength. Twelve-week-old C57BL/6N female mice were treated by the Porcupine inhibitors LGK974 (low dose = 3 mg/kg/day; high dose = 6 mg/kg/day) or Wnt-C59 (10 mg/kg/day) or vehicle for 3 weeks. Bone parameters were assessed by serum biomarkers, dual-energy X-ray absorptiometry, µCT and histomorphometry. Bone strength was measured by the 3-point bending test. The Porcupine inhibitors were well tolerated demonstrated by normal body weight. Both doses of LGK974 and Wnt-C59 reduced total body bone mineral density compared with vehicle treatment (P < 0.001). Cortical thickness of the femur shaft (P < 0.001) and trabecular bone volume fraction in the vertebral body (P < 0.001) were reduced by treatment with LGK974 or Wnt-C59. Porcupine inhibition reduced bone strength in the tibia (P < 0.05). The cortical bone loss was the result of impaired periosteal bone formation and increased endocortical bone resorption and the trabecular bone loss was caused by reduced trabecular bone formation and increased bone resorption. Porcupine inhibitors exert deleterious effects on bone mass and strength caused by a combination of reduced bone formation and increased bone resorption. We suggest that cancer targeted therapies using Porcupine inhibitors may increase the risk of fractures.

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Enhancement of Osteoclastic Bone Resorption and Suppression of Osteoblastic Bone Formation in Response to Reduced Mechanical Stress Do Not Occur in the Absence of Osteopontin

Journal of Experimental Medicine ◽

10.1084/jem.193.3.399 ◽

2001 ◽

Vol 193 (3) ◽

pp. 399-404 ◽

Cited By ~ 167

Author(s):

Muneaki Ishijima ◽

Susan R. Rittling ◽

Teruhito Yamashita ◽

Kunikazu Tsuji ◽

Hisashi Kurosawa ◽

...

Keyword(s):

Bone Resorption ◽

Bone Loss ◽

Bone Formation ◽

Mechanical Stress ◽

Bone Matrix ◽

Osteoclastic Bone Resorption ◽

Tail Suspension ◽

Wild Type ◽

Osteoblastic Bone Formation

Reduced mechanical stress to bone in bedridden patients and astronauts leads to bone loss and increase in fracture risk which is one of the major medical and health issues in modern aging society and space medicine. However, no molecule involved in the mechanisms underlying this phenomenon has been identified to date. Osteopontin (OPN) is one of the major noncollagenous proteins in bone matrix, but its function in mediating physical-force effects on bone in vivo has not been known. To investigate the possible requirement for OPN in the transduction of mechanical signaling in bone metabolism in vivo, we examined the effect of unloading on the bones of OPN−/− mice using a tail suspension model. In contrast to the tail suspension–induced bone loss in wild-type mice, OPN−/− mice did not lose bone. Elevation of urinary deoxypyridinoline levels due to unloading was observed in wild-type but not in OPN−/− mice. Analysis of the mechanisms of OPN deficiency–dependent reduction in bone on the cellular basis resulted in two unexpected findings. First, osteoclasts, which were increased by unloading in wild-type mice, were not increased by tail suspension in OPN−/− mice. Second, measures of osteoblastic bone formation, which were decreased in wild-type mice by unloading, were not altered in OPN−/− mice. These observations indicate that the presence of OPN is a prerequisite for the activation of osteoclastic bone resorption and for the reduction in osteoblastic bone formation in unloaded mice. Thus, OPN is a molecule required for the bone loss induced by mechanical stress that regulates the functions of osteoblasts and osteoclasts.

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