Oligomeric proanthocyanidins ameliorates osteoclastogenesis through reducing OPG/RANKL ratio in chicken's embryos

Poultry Science, Год журнала: 2024, Номер 103(6), С. 103706 - 103706

Опубликована: Март 30, 2024

Skeletal disorders can seriously threaten the health and performance of poultry, such as tibial dyschondroplasia (TD) osteoporosis (OP). Oligomeric proanthocyanidins (OPC) are naturally occurring polyphenolic flavonoid compounds that be used potential substances to improve bone growth poultry. Eighty 7-day-old green-eggshell yellow feather layer chickens were randomly divided into four groups: basal diet supplementation with 25, 50 100 mg/kg OPC. The results have indicated parameters significantly improved OPC in vivo, including volume (BV), mineral density (BMD) activities antioxidative enzymes, but ratio osteoprotegerin (OPG)/receptor activator NF-κB (RANK) ligand (RANKL) was decreased. Furthermore, primary marrow mesenchymal stem cells (BMSCs) monocytes/macrophages (BMMs) successfully isolated from femur tibia chickens, co-cultured differentiate osteoclasts vitro. osteogenic differentiation derived BMSCs promoted treatment high concentrations (10, 20 40 µmol/L) groups vitro, emerging inhibition osteoclastogenesis by increasing OPG/RANKL. In contrary, also low (2.5, 5 10 groups, enhanced decreasing OPG/RANKL addition, activity inhibited OPG autophagy Dietary alter balance osteoblast osteoclast, thereby improving chickens.

Язык: Английский

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FAM98 Family Proteins Play Distinct Roles in Osteoclastogenesis and Bone Resorption

Biology, Год журнала: 2025, Номер 14(1), С. 45 - 45

Опубликована: Янв. 9, 2025

There are three FAM98 family proteins (FAM98A/B/C) in humans and mice. Their physiological functions remain largely unknown. We have previously reported that Fam98a interacts with Plekhm1 murine osteoclasts lysosome trafficking/secretion bone resorption vitro. In this study, we found all Fam98 genes were expressed precursor mature osteoclasts. While the knockdown of Fam98c by a specific short-hairpin RNA (shRNA) osteoclast precursors attenuated osteoclastogenesis, depletion Fam98b an shRNA specifically disrupted trafficking phenotypes similar to shRNA-knockdown our previous study. Loss myeloid was dispensable for trabecular cortical mass mice, as well osteoclastogenesis/bone vitro, possibly due compensation increased expression Fam98a-null These findings indicate play distinct roles osteoclastogenesis function need further investigation future studies.

Язык: Английский

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Geranylgeranyl diphosphate synthase inhibition impairs osteoclast differentiation, morphology and resorptive activity

JBMR Plus, Год журнала: 2024, Номер 9(1)

Опубликована: Окт. 23, 2024

Abstract Nitrogen bisphosphonates, such as zoledronic acid, target the enzyme farnesyl diphosphate synthase (FDPS) in isoprenoid biosynthetic pathway (IBP), and are frontline treatment for osteolytic bone diseases. A strong affinity of these agents limits their distribution out skeleton. Geranylgeranyl (GGDPS) is directly downstream to FDPS IBP novel GGDPS inhibitors RAM2061 have been shown key drug-like features including prolonged half-life, metabolic stability, systemic distribution. Furthermore, exerts anti-neoplastic benefits mouse models multiple myeloma Ewing sarcoma. Therefore, we interested determining potential impact on osteoclast biology remodeling. Studies utilizing undifferentiated RAW264.7 cells demonstrated that with depletes geranylgeranyl diphosphate, impairs protein geranylgeranylation, induces markers unfolded response apoptosis. Differentiation mature osteoclasts disrupted by RAM2061, resulting decreased numbers osteoclasts, altered morphology, tartrate-resistant acid phosphatase activity. Treatment fully differentiated led resorptive Confocal microscopy studies revealed disrupts Cdc42 localization, inhibiting proper actin ring formation osteoclasts. No significant turnover or histomorphology was observed following a 3-week CD-1 mice although were observed. Liquid chromatography-tandem mass spectrometry confirmed accumulation from vivo well hydroxyapatite binding vitro. In conclusion, first demonstrate anti-osteoclastic activity inhibitor support future exploring therapeutic benefit this therapy setting pathological

Язык: Английский

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The emerging role of Rab proteins in osteoclast organelle biogenesis and function

Biochemical Society Transactions, Год журнала: 2024, Номер unknown

Опубликована: Дек. 6, 2024

Rab GTPase proteins have been extensively studied for their roles in regulating vesicle and organelle dynamics. Among the ∼60 subtypes mammalian cells, several Rabs reported to play crucial osteoclast biogenesis function. In this review, we aim provide an update on recently described GTPases, Rab11, Rab32, Rab44, Rab38, as well Rab7, Rab3D Rab27A formation

Язык: Английский

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