1,25(OH)2D deficiency induces temporomandibular joint osteoarthritis via secretion of senescence-associated inflammatory cytokines

Shen, Ming; Luo, Yuqian; Niu, Yu‐Ming; Chen, Lulu; Yuan, Xiaoqin; Goltzman, David; Chen, Ning; Miao, Dengshun

doi:10.1016/j.bone.2013.04.015

Cited by 44 publications

(42 citation statements)

References 49 publications

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“…15 Afterwards, tissues were dehydrated and embedded in paraffin, after which 5-lm sections were cut on a rotary microtome. 28 Plasmids and lentiviral transfection A modified lentiviral plasmid pCDH (mpCDH), which has both green fluorescent protein (GFP) and red fluorescent protein (RFP) cassettes, was generated based on lentiviral plasmid pCDH-CMV-MCS-EF1-copGFP (System Bioscience, Palo Alto, CA), and used as the short hairpin RNA (shRNA) expressing lentiviral vector. 27 Immunohistochemistry Immunohistochemical staining was carried out for Ki-67, phosphorylation of histone H2AX on Ser139 (g-H2AX), SOD2, 8-hydroxy-2 0 -deoxyguanosine (8-OHdG) and C-met using the avidin-biotin-peroxidase complex technique with affinity-purified antibodies of Ki-67 (Abcam, Cambridge, MA, USA), g-H2AX (Cell Signaling Technology), SOD2 (Novus Biological), 8-OHdG (Novus Biological), c-Met (Cell Signaling Technology) as we previously described.…”

Section: Histopathologymentioning

confidence: 99%

1,25‐Dihydroxy vitamin D prevents tumorigenesis by inhibiting oxidative stress and inducing tumor cellular senescence in mice

Chen

Yang

Qiao

et al. 2018

Intl Journal of Cancer

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Human epidemiological studies suggest that 1,25(OH) D deficiency might increase cancer incidence, but no spontaneous tumors have been reported in mice lacking 1,25(OH) D or deficient in its receptor. In our study, we detected, for the first time, diverse types of spontaneous tumors in l,25(OH) D deficient mice more than 1 year of age. This was associated with increased oxidative stress, cellular senescence and senescence-associated secretory phenotype molecules, such as hepatocyte growth factor, mediated via its receptor c-Met. Furthermore, 1,25(OH) D prevented spontaneous tumor development. We also demonstrated that l,25(OH) D deficiency accelerates allograft tumor initiation and growth by increasing oxidative stress and DNA damage, activating oncogenes, inactivating tumor suppressor genes, stimulating malignant cell proliferation and inhibiting their senescence; in contrast, supplementation with exogenous l,25(OH) D or antioxidant, or knock-down of the Bmi1 or c-Met oncogene, largely rescued the phenotypes of allograft tumors. Results from our study suggest that 1,25(OH) D deficiency enhances tumorigenesis by increasing malignant cell oxidative stress and DNA damage, stimulating microenvironmental cell senescence and a senescence-associated secretory phenotype, and activating oncogenes and inactivating tumor suppressor genes, thus increasing malignant cell proliferation. Our study provides direct evidence supporting the role of vitamin D deficiency in increasing cancer incidence. Conversely, 1,25(OH) D prevented spontaneous tumor development, suggesting that this inhibitory effect prevents the initiation and progression of tumorigenesis, thus provides a mechanistic basis for 1,25(OH) D to prevent tumorigenesis in an aging organism.

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Section: Histopathologymentioning

confidence: 99%

1,25‐Dihydroxy vitamin D prevents tumorigenesis by inhibiting oxidative stress and inducing tumor cellular senescence in mice

Chen

Yang

Qiao

et al. 2018

Intl Journal of Cancer

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“…(22)(23)(24) Mechanical bone marrow ablation (BMX), which causes injuryinduced intramembranous bone formation in the marrow cavity, is a well-known experimental model to rapidly study the function of genes in bone formation and remodeling in vivo. (25)(26)(27)(28)(29)(30) BMX activates a series of responses in the marrow cavity, including hematoma formation with inflammation and angiogenesis, mesenchymal cell migration and proliferation, osteogenic differentiation, and formation of new trabecular bone, followed by osteoclastic bone resorption and bone marrow reconstruction. (30) In this study, we evaluated the effects of activated FGFR2 (P253R) on bone formation and remodeling by using the BMX model in mice with inducible activation of FGFR2 (P253R) at the adult stage.…”

Section: Introductionmentioning

confidence: 99%

Inducible Activation of FGFR2 in Adult Mice Promotes Bone Formation After Bone Marrow Ablation

Luo

Wang

et al. 2017

Journal of Bone and Mineral Research

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Apert syndrome is one of the most severe craniosynostoses, resulting from gain-of-function mutations in fibroblast growth factor receptor 2 (FGFR2). Previous studies have shown that gain-of-function mutations of FGFR2 (S252W or P253R) cause skull malformation of human Apert syndrome by affecting both chondrogenesis and osteogenesis, underscoring the key role of FGFR2 in bone development. However, the effects of FGFR2 on bone formation at the adult stage have not been fully investigated. To investigate the role of FGFR2 in bone formation, we generated mice with tamoxifen-inducible expression of mutant FGFR2 (P253R) at the adult stage. Mechanical bone marrow ablation (BMX) was performed in both wild-type and Fgfr2 mutant (MT) mice. Changes in newly formed trabecular bone were assessed by micro-computed tomography and bone histomorphometry. We found that MT mice exhibited increased trabecular bone formation and decreased bone resorption after BMX accompanied with a remarkable increase in bone marrow stromal cell recruitment and proliferation, osteoblast proliferation and differentiation, and enhanced Wnt/β-catenin activity. Furthermore, pharmacologically inhibiting Wnt/β-catenin signaling can partially reverse the increased trabecular bone formation and decreased bone resorption in MT mice after BMX. Our data demonstrate that gain-of-function mutation in FGFR2 exerts a Wnt/β-catenin-dependent anabolic effect on trabecular bone by promoting bone formation and inhibiting bone resorption at the adult stage. © 2017 American Society for Bone and Mineral Research.

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“…Reductions of serum calcium levels and of serum phosphorus levels may independently influence normal skeletal metabolism. Therefore, to assess whether the hypocalcemia and hypophosphatemia in 1α(OH)ase −/− mice contributed to the periodontal defects in our animals, we maintained some mice on a rescue diet which normalizes serum calcium and phosphorus levels . We also provided the same rescue diet to the control wild‐type mice since it did not change their already normal serum calcium and phosphorus levels .…”

Section: Discussionmentioning

confidence: 99%

“…In contrast to long bones with increased trabecular bone volume and osteoblast number, the dental volume and mandibular bone volume were reduced significantly in 6‐week‐old 1α(OH)ase −/‐ mice on a normal diet, which indicated that 1,25(OH) 2 D plays a more dominant role than parathyroid hormone (PTH) in hard tissue formation in mandibles . We also previously demonstrated that 1,25(OH) 2 D deficiency causes an erosive osteoarthritis (OA) of the temporomandibular joint (TMJ) by inducing DNA damage, cellular senescence and the production of senescence‐associated inflammatory cytokines, which indicated that 1,25(OH) 2 D has a profound effect on preventing the development and progression of OA . However, it is unclear whether endogenous 1,25(OH) 2 D deficiency would result in defects in periodontal tissues, therefore contributing to the development and progression of periodontitis and osteoporosis in the jaw.…”

Section: Introductionmentioning

confidence: 99%

1,25‐dihydroxyvitamin D deficiency accelerates alveolar bone loss independent of aging and extracellular calcium and phosphorus

Gong

Chen

et al. 2018

Journal of Periodontology

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1,25(OH)2D deficiency induces temporomandibular joint osteoarthritis via secretion of senescence-associated inflammatory cytokines

Cited by 44 publications

References 49 publications

1,25‐Dihydroxy vitamin D prevents tumorigenesis by inhibiting oxidative stress and inducing tumor cellular senescence in mice

1,25‐Dihydroxy vitamin D prevents tumorigenesis by inhibiting oxidative stress and inducing tumor cellular senescence in mice

Inducible Activation of FGFR2 in Adult Mice Promotes Bone Formation After Bone Marrow Ablation

1,25‐dihydroxyvitamin D deficiency accelerates alveolar bone loss independent of aging and extracellular calcium and phosphorus

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