scholarly journals Weaning Triggers a Decrease in Receptor Activator of Nuclear Factor-κB Ligand Expression, Widespread Osteoclast Apoptosis, and Rapid Recovery of Bone Mass after Lactation in Mice

Endocrinology ◽  
2007 ◽  
Vol 148 (8) ◽  
pp. 3875-3886 ◽  
Author(s):  
Laleh Ardeshirpour ◽  
Pamela Dann ◽  
Douglas J. Adams ◽  
Tracey Nelson ◽  
Joshua VanHouten ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Formation ◽  
Bone Mass ◽  
Bone Turnover ◽  
Nuclear Factor Κb ◽  
Rapid Recovery ◽  
Rapid Decline ◽  
Nuclear Factor ◽  
Receptor Activator ◽  
Osteoclast Apoptosis

A significant portion of milk calcium comes from the mother’s skeleton, and lactation is characterized by rapid bone loss. The most remarkable aspect of this bone loss is its complete reversibility, and the time after weaning is the most rapid period of skeletal anabolism in adults. Despite this, little is known of the mechanisms by which the skeleton repairs itself after lactation. We examined changes in bone and calcium metabolism defining the transition from bone loss to bone recovery at weaning in mice. Bone mass decreases during lactation and recovers rapidly after weaning. Lactation causes changes in bone microarchitecture, including thinning and perforation of trabecular plates that are quickly repaired after weaning. Weaning causes a rapid decline in urinary C-telopeptide levels and stimulates an increase in circulating levels of osteocalcin. Bone histomorphometry documented a significant reduction in the numbers of osteoclasts on d 3 after weaning caused by a coordinated wave of osteoclast apoptosis beginning 48 h after pup removal. In contrast, osteoblast numbers and bone formation rates, which are elevated during lactation, remain so 3 d after weaning. The cessation of lactation stimulates an increase in circulating calcium levels and a reciprocal decrease in PTH levels. Finally, weaning is associated with a decrease in levels of receptor activator of nuclear factor-κB ligand mRNA in bone. In conclusion, during lactation, bone turnover is elevated, and bone loss is rapid. Weaning causes selective apoptosis of osteoclasts halting bone resorption. The sudden shift in bone turnover favoring bone formation subsequently contributes to the rapid recovery of bone mass.

scholarly journals The Fungal Metabolite (+)-Terrein Abrogates Ovariectomy-Induced Bone Loss and Receptor Activator of Nuclear Factor-κB Ligand–Induced Osteoclastogenesis by Suppressing Protein Kinase-C α/βII Phosphorylation

2021 ◽  
Vol 12 ◽  
Author(s):  
Kyosuke Sakaida ◽  
Kazuhiro Omori ◽  
Masaaki Nakayama ◽  
Hiroki Mandai ◽  
Saki Nakagawa ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Mass ◽  
Bone Metabolism ◽  
Osteoclast Differentiation ◽  
Nuclear Factor Κb ◽  
Common Disease ◽  
Mouse Bone Marrow ◽  
Nuclear Factor ◽  
Receptor Activator

Osteoporosis is a common disease characterized by a systemic impairment of bone mass and microarchitecture that results in fragility fractures. Severe bone loss due to osteoporosis triggers pathological fractures and consequently decreases the daily life activity and quality of life. Therefore, prevention of osteoporosis has become an important issue to be addressed. We have reported that the fungal secondary metabolite (+)-terrein (TER), a natural compound derived from Aspergillus terreus, has shown receptor activator of nuclear factor-κB ligand (RANKL)–induced osteoclast differentiation by suppressing nuclear factor of activated T-cell 1 (NFATc1) expression, a master regulator of osteoclastogenesis. TER has been shown to possess extensive biological and pharmacological benefits; however, its effects on bone metabolism remain unclear. In this study, we investigated the effects of TER on the femoral bone metabolism using a mouse-ovariectomized osteoporosis model (OVX mice) and then on RANKL signal transduction using mouse bone marrow macrophages (mBMMs). In vivo administration of TER significantly improved bone density, bone mass, and trabecular number in OVX mice (p < 0.01). In addition, TER suppressed TRAP and cathepsin-K expression in the tissue sections of OVX mice (p < 0.01). In an in vitro study, TER suppressed RANKL-induced phosphorylation of PKCα/βII, which is involved in the expression of NFATc1 (p < 0.05). The PKC inhibitor, GF109203X, also inhibited RANKL-induced osteoclastogenesis in mBMMs as well as TER. In addition, TER suppressed the expression of osteoclastogenesis-related genes, such as Ocstamp, Dcstamp, Calcr, Atp6v0d2, Oscar, and Itgb3 (p < 0.01). These results provide promising evidence for the potential therapeutic application of TER as a novel treatment compound against osteoporosis.

Prolactin directly enhances bone turnover by raising osteoblast-expressed receptor activator of nuclear factor κB ligand/osteoprotegerin ratio

Bone ◽  
2008 ◽  
Vol 42 (3) ◽  
pp. 535-546 ◽  
Author(s):  
Dutmanee Seriwatanachai ◽  
Kanogwun Thongchote ◽  
Narattaphol Charoenphandhu ◽  
Jantarima Pandaranandaka ◽  
Kukiat Tudpor ◽  
...  
Keyword(s):  
Bone Turnover ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Receptor Activator

scholarly journals Lack of NOD2 attenuates ovariectomy-induced bone loss via inhibition of osteoclasts

2017 ◽  
Vol 235 (2) ◽  
pp. 85-96 ◽  
Author(s):  
Ke Ke ◽  
Ok-Joo Sul ◽  
Soo-Wol Chung ◽  
Jae-Hee Suh ◽  
Hye-Seon Choi
Keyword(s):  
Bone Loss ◽  
Nuclear Factor Kappa B ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Nuclear Factor Κb ◽  
Innate Immune ◽  
Nuclear Factor ◽  
Oxygen Species ◽  
Receptor Activator ◽  
Recognition Receptor ◽  
Oligomerization Domain

Nucleotide-binding oligomerization domain-2 (NOD2) is a pattern recognition receptor of the innate immune system. It interacts with serine–threonine kinases to induce activation of nuclear factor κB (NF-κB), which is important for receptor activator of nuclear factor kappa-B ligand (RANKL) signaling. We tested the idea that NOD2 modulates bone metabolism via an action on osteoclasts (OCs). The absence of NOD2 reduced ovariectomy-induced bone loss in mice, and lowered the area and the activity of OCs, by impairing RANKL signaling. It also reduced the level of reactive oxygen species (ROS), as well as of NF-κB-DNA binding upon RANKL exposure. NOD2 was found to physically interact with nicotinamide adenine dinucleotide phosphate oxidase 1, and this led to increased production of ROS in OCs. Our data suggest that NOD2 contributes to bone loss in estrogen deficiency by elevating ROS levels in OCs.

scholarly journals T-cell receptor activator of nuclear factor-κB ligand/osteoprotegerin imbalance is associated with HIV-induced bone loss in patients with higher CD4+ T-cell counts

AIDS ◽  
2018 ◽  
Vol 32 (7) ◽  
pp. 885-894 ◽  
Author(s):  
Kehmia Titanji ◽  
Aswani Vunnava ◽  
Antonina Foster ◽  
Anandi N. Sheth ◽  
Jeffrey L. Lennox ◽  
...  
Keyword(s):  
T Cell ◽  
Bone Loss ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Nuclear Factor Κb ◽  
Cd4 T Cell ◽  
Nuclear Factor ◽  
Cell Counts ◽  
Receptor Activator

Retrovirus-Mediated Gene Transfer of Receptor Activator of Nuclear Factor-κB-Fc Prevents Bone Loss in Ovariectomized Mice

Stem Cells ◽  
2006 ◽  
Vol 24 (7) ◽  
pp. 1798-1805 ◽  
Author(s):  
Dohee Kim ◽  
Sun Wook Cho ◽  
Sun Ju Her ◽  
Jae Yun Yang ◽  
Sang Wan Kim ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Bone Loss ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Ovariectomized Mice ◽  
Receptor Activator

scholarly journals Absence of Herpes Virus Entry Mediator (HVEM) Increases Bone Mass by Attenuating Receptor Activator of Nuclear Factor-κB ligand (RANKL)-Induced Osteoclastogenesis

Endocrinology ◽  
2012 ◽  
Vol 153 (10) ◽  
pp. 4808-4817 ◽  
Author(s):  
Woon-Ki Kim ◽  
Ok-Joo Sul ◽  
Eun-Kyung Choi ◽  
Mi-Hyun Lee ◽  
Choon-Soo Jeong ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Mass ◽  
Knockout Mice ◽  
Herpes Virus ◽  
Virus Entry ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Herpes Virus Entry Mediator ◽  
Receptor Activator ◽  
Herpès Virus

Abstract Herpes virus entry mediator (HVEM), which is constitutively expressed at a high level on myeloid lineage cells, is also expressed on bone marrow-derived macrophages, suggesting that it may play a role in bone metabolism by affecting osteoclasts (OC) derived from bone marrow-derived macrophages. To address this question, we evaluated bone mass by micro-computed tomography and the number and activity of OC by tartrate-resistant acid phosphatase (TRAP) and pit formation on dentine slices, comparing HVEM-knockout mice with wild-type mice. The absence of HVEM led to a higher bone mass and to decreased levels of serum collagen type I fragments and serum TRACP5b in vivo. In vitro HVEM deficiency resulted in a reduced number and activity of OC and an impaired receptor activator of nuclear factor-κB ligand signaling through reduced activation of nuclear factor-κB and of nuclear factor of activated T-cells cytoplasmic 1. Exogenous soluble HVEM decreased expression of TRAP, whereas soluble LIGHT (a ligand of HVEM) increased it, indicating the occurrence of a positive signaling through HVEM during osteoclastogenesis. Our findings indicate that HVEM regulates bone remodeling via action on OC. The higher bone mass in the femurs of HVEM-knockout mice could be, at least in part, due to attenuated osteoclastogenesis and bone resorption resulting from decreased receptor activator of nuclear factor-κB ligand signaling in the OC.

scholarly journals Prolactin blocks the expression of receptor activator of nuclear factor κB ligand and reduces osteoclastogenesis and bone loss in murine inflammatory arthritis

2017 ◽  
Vol 19 (1) ◽  
Author(s):  
Maria G. Ledesma-Colunga ◽  
Norma Adán ◽  
Georgina Ortiz ◽  
Mariana Solís-Gutiérrez ◽  
Fernando López-Barrera ◽  
...  
Keyword(s):  
Bone Loss ◽  
Inflammatory Arthritis ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Receptor Activator
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