Deletion of IL-17ra in osteoclast precursors increases bone mass by decreasing osteoclast precursor abundance

Bone ◽  
2021 ◽  
pp. 116310
Author(s):  
Joseph L. Roberts ◽  
Giovanni Mella-Velazquez ◽  
Hamid Y. Dar ◽  
Guanglu Liu ◽  
Hicham Drissi
Keyword(s):  
Bone Mass ◽  
Osteoclast Precursor ◽  
Osteoclast Precursors

scholarly journals GPR109A mediates the effects of hippuric acid on regulating osteoclastogenesis and bone resorption in mice

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Jin-Ran Chen ◽  
Haijun Zhao ◽  
Umesh D. Wankhade ◽  
Sree V. Chintapalli ◽  
Can Li ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Resorption ◽  
Bone Mass ◽  
Hippuric Acid ◽  
Ex Vivo ◽  
Marrow Cell ◽  
Osteoclast Differentiation ◽  
Bone Homeostasis ◽  
Wild Type ◽  
Osteoclast Precursors

AbstractThe G protein-coupled receptor 109 A (GPR109A) is robustly expressed in osteoclastic precursor macrophages. Previous studies suggested that GPR109A mediates effects of diet-derived phenolic acids such as hippuric acid (HA) and 3-(3-hydroxyphenyl) propionic acid (3-3-PPA) on promoting bone formation. However, the role of GPR109A in metabolic bone homeostasis and osteoclast differentiation has not been investigated. Using densitometric, bone histologic and molecular signaling analytic methods, we uncovered that bone mass and strength were significantly higher in tibia and spine of standard rodent diet weaned 4-week-old and 6-month-old GPR109A gene deletion (GPR109A−/−) mice, compared to their wild type controls. Osteoclast numbers in bone and in ex vivo bone marrow cell cultures were significantly decreased in GPR109A−/− mice compared to wild type controls. In accordance with these data, CTX-1 in bone marrow plasma and gene expression of bone resorption markers (TNFα, TRAP, Cathepsin K) were significantly decreased in GPR109A−/− mice, while on the other hand, P1NP was increased in serum from both male and female GPR109A−/− mice compared to their respective controls. GPR109A deletion led to suppressed Wnt/β-catenin signaling in osteoclast precursors to inhibit osteoclast differentiation and activity. Indeed, HA and 3-3-PPA substantially inhibited RANKL-induced GPR109A expression and Wnt/β-catenin signaling in osteoclast precursors and osteoclast differentiation. Resultantly, HA significantly inhibited bone resorption and increased bone mass in wild type mice, but had no additional effects on bone in GPR109A−/− mice compared with their respective untreated control mice. These results suggest an important role for GPR109A during osteoclast differentiation and bone resorption mediating effects of HA and 3-3-PPA on inhibiting bone resorption during skeletal development.

scholarly journals PI3K activation increases SDF-1 production and number of osteoclast precursors, and enhances SDF-1-mediated osteoclast precursor migration

Bone Reports ◽  
2019 ◽  
Vol 10 ◽  
pp. 100203
Author(s):  
Naga Suresh Adapala ◽  
Sierra Root ◽  
Joseph Lorenzo ◽  
Hector Aguila ◽  
Archana Sanjay
Keyword(s):  
Osteoclast Precursor ◽  
Osteoclast Precursors ◽  
Pi3k Activation

scholarly journals Anti-c-fms Antibody Prevents Osteoclast Formation and Bone Resorption in Co-Culture of Osteoblasts and Osteoclast Precursors In Vitro and in Ovariectomized Mice

2020 ◽  
Vol 21 (17) ◽  
pp. 6120
Author(s):  
Yasuhiko Nara ◽  
Hideki Kitaura ◽  
Saika Ogawa ◽  
Wei-Ren Shen ◽  
Jiawei Qi ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Structure ◽  
Osteoclast Differentiation ◽  
Osteoclast Formation ◽  
Osteoclast Precursor ◽  
Antibody Treatment ◽  
Osteoporosis Therapy ◽  
Osteoclast Precursors ◽  
Ovariectomized Mice

Osteoporosis morphology is characterized by bone resorption and decreases in micro-architecture parameters. Anti-osteoporosis therapy targets osteoclasts because bone resorption is a unique function of osteoclasts. Anti-c-fms antibodies against the receptor for macrophage colony-stimulating factor (M-CSF) inhibit osteoclast formation and bone resorption in vitro and in vivo. However, the effect of anti-c-fms antibodies on bone resorption in ovariectomized (OVX) mice is unknown. In this study, we evaluated the effect of anti-c-fms antibodies on osteoclast formation and bone resorption in osteoblast–osteoclast precursor co-culture in vitro and in OVX mice. Osteoblast and osteoclast precursor co-cultures treated with anti-c-fms antibodies showed significantly inhibited osteoclast formation, while cultures without anti-c-fms antibody treatment showed osteoclast formation. However, anti-c-fms antibodies did not change the receptor activator of nuclear factor kappa-B ligand (RANKL) or osteoprotegrin (OPG) expression during osteoblast and osteoclast differentiation in vitro. These results indicate that anti-c-fms antibodies directly affected osteoclast formation from osteoclast precursors in co-culture. OVX mice were treated with intraperitoneal injections of anti-c-fms antibody. The trabecular bone structure of the femur was assessed by micro-computer tomography. The anti-c-fms antibody inhibited osteoclast formation and bone loss compared with PBS-treated OVX mice. These results indicate potential for the therapeutic application of anti-c-fms antibodies for postmenopausal osteoporosis.

Oxysterols and EBI2 promote osteoclast precursor migration to bone surfaces and regulate bone mass homeostasis

2015 ◽  
Vol 211 (1) ◽  
pp. 2111OIA228
Author(s):  
Erin Nevius ◽  
Flavia Pinho ◽  
Meera Dhodapkar ◽  
Huiyan Jin ◽  
Kristina Nadrah ◽  
...  
Keyword(s):  
Bone Mass ◽  
Osteoclast Precursor

scholarly journals Runx1 Regulates Myeloid Precursor Differentiation Into Osteoclasts Without Affecting Differentiation Into Antigen Presenting or Phagocytic Cells in Both Males and Females

Endocrinology ◽  
2016 ◽  
Vol 157 (8) ◽  
pp. 3058-3069 ◽  
Author(s):  
David N. Paglia ◽  
Xiaochuan Yang ◽  
Judith Kalinowski ◽  
Sandra Jastrzebski ◽  
Hicham Drissi ◽  
...  
Keyword(s):  
Bone Mass ◽  
Volume Fraction ◽  
Myeloid Cell ◽  
Antigen Presenting Cells ◽  
Osteoclast Formation ◽  
Precursor Cells ◽  
Phagocytic Cells ◽  
Bone Volume Fraction ◽  
Osteoclast Precursors ◽  
Antigen Presenting

Runt-related transcription factor 1 (Runx1), a master regulator of hematopoiesis, is expressed in preosteoclasts. Previously we evaluated the bone phenotype of CD11b-Cre Runx1fl/fl mice and demonstrated enhanced osteoclasts and decreased bone mass in males. However, an assessment of the effects of Runx1 deletion in female osteoclast precursors was impossible with this model. Moreover, the role of Runx1 in myeloid cell differentiation into other lineages is unknown. Therefore, we generated LysM-Cre Runx1fl/fl mice, which delete Runx1 equally (∼80% deletion) in myeloid precursor cells from both sexes and examined the capacity of these cells to differentiate into osteoclasts and phagocytic and antigen-presenting cells. Both female and male LysM-Cre Runx1fl/fl mice had decreased trabecular bone mass (72% decrease in bone volume fraction) and increased osteoclast number (2–3 times) (P < .05) without alteration of osteoblast histomorphometric indices. We also demonstrated that loss of Runx1 in pluripotential myeloid precursors with LysM-Cre did not alter the number of myeloid precursor cells in bone marrow or their ability to differentiate into phagocytizing or antigen-presenting cells. This study demonstrates that abrogation of Runx1 in multipotential myeloid precursor cells significantly and specifically enhanced the ability of receptor activator of nuclear factor-κB ligand to stimulate osteoclast formation and fusion in female and male mice without affecting other myeloid cell fates. In turn, increased osteoclast activity in LysM-Cre Runx1fl/fl mice likely contributed to a decrease in bone mass. These dramatic effects were not due to increased osteoclast precursors in the deleted mutants and argue that inhibition of Runx1 in multipotential myeloid precursor cells is important for osteoclast formation and function.

Does short-term administration of glucagon-like peptide type 2 affect bone mass and markers of bone remodeling in short bowel patients?

2001 ◽  
Vol 120 (5) ◽  
pp. A314-A314
Author(s):  
K HADERSLEV ◽  
P JEPPESEN ◽  
B HARTMANN ◽  
J THULESEN ◽  
J GRAFF ◽  
...  
Keyword(s):  
Bone Mass ◽  
Bone Remodeling ◽  
Short Term ◽  
Short Bowel ◽  
Term Administration ◽  
Glucagon Like Peptide

Kontrazeption zu Beginn und Ende der fertilen Lebensphase

2009 ◽  
Vol 66 (2) ◽  
pp. 109-115 ◽  
Author(s):  
Joseph Neulen ◽  
Christian Thaler ◽  
Martin Birkhäuser ◽  
Wilhelm Braendle ◽  
Paul J. Keller ◽  
...  
Keyword(s):  
Bone Mass ◽  
Peak Bone Mass ◽  
Arterielle Hypertonie

Die Nutzen-/Risiko-Bilanz einer hormonalen Kontrazeption (OH) ist sowohl bei Jugendlichen als auch bei der Frau über 40 Jahren günstig, sofern bestimmte Regeln beachtet werden. Bei Jugendlichen betrifft dies insbesondere den Ermöglichung des Erwerbs einer normalen Peak-Bone-Mass durch die Wahl eines korrekt dosierten OH, bei älteren Frauen den aktiven Ausschluss von Kontraindikationen wie arterielle Hypertonie, Adipositas, Rauchen und Dyslipidämie. In beiden Altersgruppen ist in jedem Falle das Risiko einer korrekt indizierten OH geringer als dasjenige einer unerwünschten Schwangerschaft.

Sign in / Sign up

Export Citation Format

Share Document