Effect of vitamin K2 on osteoblast apoptosis: Vitamin K2 inhibits apoptotic cell death of human osteoblasts induced by Fas, proteasome inhibitor, etoposide, and staurosporine

Urayama, Satoshi; Kawakami, Atsushi; Nakashima, Tomoki; Tsuboi, Masahiko; Yamasaki, Satoshi; Hida, Ayumi; Ichinose, Yasufumi; Nakamura, Hideki; Ejima, Eri; Aoyagi, Takahiko; Nakamura, Tatsufumi; Migita, Kiyoshi; Kawabe, Yojiro; Eguchi, Katsumi

doi:10.1067/mlc.2000.108754

Cited by 59 publications

(37 citation statements)

References 34 publications

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“…Vitamin K 2 decreases bone resorption by inhibiting the formation of osteoclasts (10) as well as their bone resorptive activity (11,12). Vitamin K 2 treatment also induces apoptosis of osteoclasts (13) while inhibiting apoptosis of osteoblasts (71) thereby shifting the balance toward bone formation. Vitamin K 2 was also shown to enhance the induction of osteocalcin mRNA levels mediated by co-administered 1␣,25-(OH) 2 vitamin D 3 (7,37).…”

Section: Discussionmentioning

confidence: 99%

Vitamin K2 Regulation of Bone Homeostasis Is Mediated by the Steroid and Xenobiotic Receptor SXR

Tabb

Sun

Zhou

et al. 2003

Journal of Biological Chemistry

338

258

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Vitamin K 2 is a critical nutrient required for blood clotting that also plays an important role in bone formation. Vitamin K 2 supplementation up-regulates the expression of bone markers, increases bone density in vivo, and is used clinically in the management of osteoporosis. The mechanism of vitamin K 2 action in bone formation was thought to involve its normal role as an essential cofactor for ␥-carboxylation of bone matrix proteins. However, there is evidence that suggests vitamin K 2 also has a transcriptional regulatory function. Vitamin K 2 bound to and activated the orphan nuclear receptor SXR and induced expression of the SXR target gene, CYP3A4, identifying it as a bona fide SXR ligand. Vitamin K 2 treatment of osteosarcoma cells increased mRNA levels for the osteoblast markers bone alkaline phosphatase, osteoprotegerin, osteopontin, and matrix Gla protein. The known SXR activators rifampicin and hyperforin induced this panel of bone markers to an extent similar to vitamin K 2 . Vitamin K 2 was able to induce bone markers in primary osteocytes isolated from wild-type murine calvaria but not in cells isolated from mice deficient in the SXR ortholog PXR. We infer that vitamin K 2 is a transcriptional regulator of bonespecific genes that acts through SXR to favor the expression of osteoblastic markers. Thus, SXR has a novel role as a mediator of bone homeostasis in addition to its role as a xenobiotic sensor. An important implication of this work is that a subset of SXR activators may function as effective therapeutic agents for the management of osteoporosis.

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Section: Discussionmentioning

confidence: 99%

Vitamin K2 Regulation of Bone Homeostasis Is Mediated by the Steroid and Xenobiotic Receptor SXR

Tabb

Sun

Zhou

et al. 2003

Journal of Biological Chemistry

338

258

View full text Add to dashboard Cite

show abstract

“…In addition, MK-4 has several unique functions such as induction of programmed cell death in osteoclasts and several tumor cells in vitro [14][15][16][17][18], inhibition of the differentiation of osteoclasts [19][20][21][22] and apoptosis in osteoblasts [23], and direct stimulation of the expression of certain genes via the activation of the nuclear receptor PXR [24][25][26]. Warfarin, which is an antagonist of Gla formation, does not inhibit the abovementioned novel effects of vitamin K; therefore, these effects of vitamin K are independent of its Gla formation activity.…”

Section: Introductionmentioning

confidence: 99%

Vitamin K suppresses the lipopolysaccharide-induced expression of inflammatory cytokines in cultured macrophage-like cells via the inhibition of the activation of nuclear factor κB through the repression of IKKα/β phosphorylation

Ohsaki

Shirakawa

Miura

et al. 2010

The Journal of Nutritional Biochemistry

147

121

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“…La vitamina K parece ejercer una inhibición parcial de la absorción del calcio en los osteoblastos al reducir la apoptosis innecesaria en estas células (8,9).…”

Section: Artículo Originalunclassified

Análisis de polimorfismos APO-E en mujeres colombianas con osteoporosis y correlación con variables clínicas y sociales de riesgo.

Villarreal¹,

Bermúdez²

2004

biomedica

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Varios estudios han demostrado la asociación de los polimorfismos de la apolipoproteína E (APO-E) con la osteoporosis, especialmente, la APO-E 4. Para analizar los polimorfismos APO-E e identificar la asociación con variables clínicas y sociales, se realizó un estudio descriptivo de 32 mujeres con osteoporosis, provenientes de diferentes regiones de Colombia, mediante metodologías PCR y RFLP. Se observaron en osteoporosis, osteopenia y osteoporosis combinada con osteopenia frecuencias para el genotipo ε3/ε3 en el 84,3% (n=27), y en el 15,6% para los genotipos con el alelo ε4 (ε3/ε4=12,5%, n=4; ε4/ε4=3,1%, n=1); la misma tendencia se observó en la distribución por edad de la menopausia, ε3/ε3 en el 83,3% (n=25), y genotipos con el alelo ε4 en el 16,6% (n=5) (ε3/ε4=13,3%, n=4; ε4/ε4=3,3%, n=1). No hubo asociación de APO-E4 con estrato socioeconómico, fracturas, enfermedades o consumo de lácteos. Aunque no hubo efecto del alelo ε4 en la densidad mineral ósea (DMO) de la columna lumbar: ε4+/-(ε3/ε4 0,960±0,144 g/cm 2 ); ε4+/+ (ε4/ε4 0,873±0,00 g/cm 2 ); ε4-/-(ε3/ε3 0,858±0,160 g/cm 2 ); p=0,49, ni en cuello femoral: ε4+/-(ε3/ε4 0,841±0,026 g/cm 2 ); ε4+/+ (ε4/ε4 0,842±0,00 g/cm 2 ); ε4-/-(ε3/ε3 0,735±0,013 g/cm 2 ), p=0,14, al explorar las diferencias de medias de DMO en el cuello femoral, se observó una diferencia significativa, t=4,17 p=0,05. Estos datos confirman una frecuencia del alelo ε4 similar a lo reportado en poblaciones caucásicas y japonesas; se sugiere realizar estudios a gran escala para esclarecer el impacto de la APO-E sobre la DMO y su relación dosis-efecto.Palabras claves: apolipoproteína E, polimorfismos, genotipos, osteoporosis, DMO, alelo. Polymorphismsof APO-E in Colombian women with osteoporosis: correlation among clinical and s9ocial risk variablesSeveral studies have reported an association between apolipoprotein E polymorphisms and osteoporosis, specially the genotype APO-E4. In order to analyze the APO-E polymorphisms and to identify their association with clinical and social variables, a descriptive study was undertaken that included 32 women with osteoporosis, from different regions of Colombia. The polymorphisms were detected by PCR and RFLP methods. In osteopenia and osteoporosis combined with osteopenia were observed the genotype ε3/ε3 in the 84% (n=27), and 16% (ε3/ε4=12,5%, n=4; ε4/ε4=3,1%, n=1) for the genotypes bearing the ε4 allele. The same tendency was observed by age of the menopause, ε3/ε3 in the 83% (n=25), and the genotypes bearing the ε4 allele in the 17% (n=5)(ε3/ε4=13,3%, n=4; ε4/ε4=3,3%, n=1). No association of APO-E4 was detected with socioeconomic stratum, fracture, illness, surgeries, and milk consumption. No significant differences were observed in the bone mineral density (BMD) of the lumbar column between the genotypes with or without the ε4 allele ε4+/-(ε3/ε4 0.96±0.14 g/cm 2 ); ε4+/+ (ε4/ε4 0.87±0.0 g/cm 2 ); ε4-/-(ε3/ε3 0.86±0.16 g/cm 2 ); p=0.49, and femoral bone mineral density ε4+/-(ε3/ε4 0.84±0.03 g/cm 2 ); ε4+/+ (ε4/ε4 0.84±0.0 g/cm 2 ); ε4-/-(ε3/ε3 0.74±0...

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Effect of vitamin K2 on osteoblast apoptosis: Vitamin K2 inhibits apoptotic cell death of human osteoblasts induced by Fas, proteasome inhibitor, etoposide, and staurosporine

Cited by 59 publications

References 34 publications

Vitamin K2 Regulation of Bone Homeostasis Is Mediated by the Steroid and Xenobiotic Receptor SXR

Vitamin K2 Regulation of Bone Homeostasis Is Mediated by the Steroid and Xenobiotic Receptor SXR

Vitamin K suppresses the lipopolysaccharide-induced expression of inflammatory cytokines in cultured macrophage-like cells via the inhibition of the activation of nuclear factor κB through the repression of IKKα/β phosphorylation

Análisis de polimorfismos APO-E en mujeres colombianas con osteoporosis y correlación con variables clínicas y sociales de riesgo.

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