Fas receptor is required for estrogen deficiency-induced bone loss in mice

Kovačić, Nataša; Grčević, Danka; Katavić, Vedran; Lukić, Ivan; Grubišić, Vladimir; Mihovilović, Karlo; Cvija, Hrvoje; Croucher, Peter I.; Marušić, Ana

doi:10.1038/labinvest.2009.144

Cited by 32 publications

(24 citation statements)

References 36 publications

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“…[7][8][9][10]15,[34][35][36][37] As osteoblast precursors/ osteoblasts express membrane-bounded FASL and osteoclasts express FAS, 23,29 osteoblast-osteoclast contact is very likely to happen during the bone remodeling process. Thus, it is reasonable to assume that osteoblast lineage cells are capable of inducing osteoclast apoptosis to serve as an alternative mechanism to govern osteoclast activity.…”

Section: Discussionmentioning

confidence: 99%

Osteoblast-induced osteoclast apoptosis by fas ligand/FAS pathway is required for maintenance of bone mass

et al. 2015

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The interplay between osteoblasts and osteoclasts has a crucial role in maintaining bone homeostasis. In this study, we reveal that osteoblasts are capable of inducing osteoclast apoptosis by FAS ligand (FASL)/FAS signaling. Conditional knockout of FASL in osteoblasts results in elevated osteoclast numbers and activity, along with reduced bone mass, suggesting that osteoblastproduced FASL is required to maintain physiological bone mass. More interestingly, we show that osteoblasts from ovariectomized (OVX) osteoporotic mice exhibit decreased FASL expression that results from the IFN-γ-and TNF-α-activated NF-κB pathway, leading to reduced osteoclast apoptosis and increased bone resorption. Systemic administration of either IFN-γ or TNF-α ameliorates the osteoporotic phenotype in OVX mice and rescues FASL expression in osteoblasts. In addition, ovariectomy induces more significant bone loss in FASL conditional knockout mice than in control group with increased osteoclast activity in which the levels of RANKL and OPG remain unchanged. Taken together, this study suggests that osteoblast-induced osteoclast apoptosis via FASL/FAS signaling is a previously unrecognized mechanism that has an important role in the maintenance of bone mass in both physiological conditions and OVX osteoporosis.

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Section: Discussionmentioning

confidence: 99%

Osteoblast-induced osteoclast apoptosis by fas ligand/FAS pathway is required for maintenance of bone mass

et al. 2015

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“…Generation of OVX mice was performed as described previously [11] and age-matched C3H/HeJ mice receiving sham operation served as control (n=8). In experimental groups (n=11), 99 Tc-MDP (Yunke, Chengdu, Sichuan, China.…”

Section: Methodsmentioning

confidence: 99%

Technetium-99 Conjugated with Methylene Diphosphonate Ameliorates Ovariectomy-Induced Osteoporotic Phenotype without Causing Osteonecrosis in the Jaw

et al. 2012

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Technetium-99 conjugated with methylene diphosphonate (99Tc-MDP) is a novel bisphosphonate derivative without radioactivity and has been successfully used to treat arthritis in China for years. Since bisphosphonate therapy has the potential to induce bisphosphonate-associated osteonecrosis of the jaw (BRONJ), we examine whether 99Tc-MDP represents a new class of bisphosphonate for anti-resorptive therapy to ameliorate estrogen deficiency–induced bone resorption with less risk of causing BRONJ. We showed that 99Tc-MDP-treated ovariectomized (OVX) mice had significantly improved bone mineral density (BMD) and trabecular bone volume in comparison to the untreated OVX group by inhibiting osteoclasts and enhancing osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs). To determine the potential of inducing BRONJ, 99Tc-MDP/dexamethasone (Dex) or zoledronate/Dex were administered into C57BL/6J mice via the tail vein, followed by extraction of maxillary first molars. Interestingly, 99Tc-MDP treatment showed less risk to induce osteonecrosis in the maxillary bones compared to zoledronate treatment group, partially because 99Tc-MDP neither suppressed adaptive regulatory T cells (Tregs) nor activated the inflammatory T-helper-producing interleukin 17 cells (Th17). Taken together, our findings demonstrate that 99Tc-MDP therapy may be a promising approach in the treatment of osteoporosis with less risk of causing BRONJ.

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“…OVX has been shown to increase osteoblast expression of Fas (CD95), a well characterized “death” receptor, resulting in suppressed osteoblast differentiation and increased apoptosis (29). Interestingly Fas-deficient mice are protected from OVX induced bone loss due to enhanced osteoblast differentiation and activity (30). …”

Section: Bone Diseasementioning

confidence: 99%

The Potential of Probiotics as a Therapy for Osteoporosis

Collins¹,

Rios‐Arce²,

Schepper³

et al. 2017

Microbiol Spectr

142

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Osteoporosis, characterized by low bone mass and micro-architectural deterioration of bone tissue with increased risk of fracture, can be categorized into two forms: primary or secondary, depending on whether it occurs as part of the natural aging process (estrogen-deficiency) or as part of disease pathology. In both forms bone loss is due to an imbalance in the bone remodeling process with resorption/formation skewed more toward bone loss. Recent studies and emerging evidence consistently demonstrate the potential of the intestinal microbiota to modulate bone health. The current chapter discusses the process of bone remodeling and the pathology of osteoporosis and introduces the intestinal microbiota and its potential to influence bone health. In particular, we highlight recent murine studies that examine how probiotic supplementation can both increase bone density in healthy individuals as well as protect against primary (estrogen-deficiency) as well as secondary osteoporosis. Potential mechanisms are described to account for how probiotic treatments could be exerting their beneficial effect on bone health.

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Fas receptor is required for estrogen deficiency-induced bone loss in mice

Cited by 32 publications

References 36 publications

Osteoblast-induced osteoclast apoptosis by fas ligand/FAS pathway is required for maintenance of bone mass

Osteoblast-induced osteoclast apoptosis by fas ligand/FAS pathway is required for maintenance of bone mass

Technetium-99 Conjugated with Methylene Diphosphonate Ameliorates Ovariectomy-Induced Osteoporotic Phenotype without Causing Osteonecrosis in the Jaw

The Potential of Probiotics as a Therapy for Osteoporosis

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