Genistein stimulates the osteoblastic differentiation via NO/cGMP in bone marrow culture

Wei Pan, Leigh Quarles, Li Hua Song, Yan Hui Yu, Chen Jiao, Hong Bo Tang, Chang Hong Jiang, Han Wu Deng, Yuan Jian Li, Hong Hao Zhou, Zhousheng Xiao

Research output: Contribution to journalArticle

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Abstract

The soybean phytoestrogen, genistein (Gen), has anabolic effects on bone through mechanisms that remain to be elucidated. We examined the role of nitric oxide (NO) and its downstream effector guanylyl cyclase (CC) in mediating the effects of Gen on the proliferation and osteoblastic maturation of primary mouse bone marrow-derived mesenchymal stem cells (BMSCs). Gen (10 -8 ∼10 -6 M) resulted in a dose-dependent increase in cell proliferation as measured by increased [ 3 H]thymidine incorporation, and stimulated osteoblastic maturation as assessed by culture duration-dependent increments in alkaline phosphatase (ALP) activity, calcium deposition into extracellular matrix and Runx2/Cbfa1 gene expression in BMSCs cultures. Gen also resulted in a dose-dependent increase in NO synthase (NOS) activity, NO formation, and cGMP production in BMSCs cultures. The effects of Gen were mimicked by 17β-estradiol (E 2 , 10 -8 M). Concurrent treatment with the estrogen receptor (ER) antagonist ICI182,780 (10 -7 M) or the NOS inhibitor L-NAME (3 × 10 -3 M) diminished the Gen (10 -6 M)-mediated increase in NOS activity, NO production, and cGMP content. In contrast, a soluble GC inhibitor 1H-[1,2,4]oxadiazolo [4,3,-a]quinoxalin-1-one (ODQ, 10 -6 M) selectively blocked the Gen(10 -6 M)-mediated increase in cGMP content but not in NO production and NOS activity. Moreover, inhibition of ER, NOS activity or cGMP blocked Gen-induced proliferation and osteoblastic differentiation of BMSCs and Runx2/Cbfa1 gene expression in culture. Gen has estrogen-like activity and stimulates the proliferation and osteoblastic differentiation of mouse BMSCs at least in part through NO/cGMP pathway.

Original languageEnglish (US)
Pages (from-to)307-316
Number of pages10
JournalJournal of Cellular Biochemistry
Volume94
Issue number2
DOIs
StatePublished - Feb 1 2005
Externally publishedYes

Fingerprint

Genistein
Nitric Oxide
Bone
Bone Marrow
Nitric Oxide Synthase
Stem cells
Mesenchymal Stromal Cells
Cell culture
Gene expression
Cell Culture Techniques
Gene Expression
Anabolic Agents
Phytoestrogens
Guanylate Cyclase
NG-Nitroarginine Methyl Ester
Cell proliferation
Soybeans
Estrogen Receptors
Thymidine
Extracellular Matrix

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Genistein stimulates the osteoblastic differentiation via NO/cGMP in bone marrow culture. / Pan, Wei; Quarles, Leigh; Song, Li Hua; Yu, Yan Hui; Jiao, Chen; Tang, Hong Bo; Jiang, Chang Hong; Deng, Han Wu; Li, Yuan Jian; Zhou, Hong Hao; Xiao, Zhousheng.

In: Journal of Cellular Biochemistry, Vol. 94, No. 2, 01.02.2005, p. 307-316.

Research output: Contribution to journalArticle

Pan, W, Quarles, L, Song, LH, Yu, YH, Jiao, C, Tang, HB, Jiang, CH, Deng, HW, Li, YJ, Zhou, HH & Xiao, Z 2005, 'Genistein stimulates the osteoblastic differentiation via NO/cGMP in bone marrow culture', Journal of Cellular Biochemistry, vol. 94, no. 2, pp. 307-316. https://doi.org/10.1002/jcb.20308
Pan, Wei ; Quarles, Leigh ; Song, Li Hua ; Yu, Yan Hui ; Jiao, Chen ; Tang, Hong Bo ; Jiang, Chang Hong ; Deng, Han Wu ; Li, Yuan Jian ; Zhou, Hong Hao ; Xiao, Zhousheng. / Genistein stimulates the osteoblastic differentiation via NO/cGMP in bone marrow culture. In: Journal of Cellular Biochemistry. 2005 ; Vol. 94, No. 2. pp. 307-316.
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abstract = "The soybean phytoestrogen, genistein (Gen), has anabolic effects on bone through mechanisms that remain to be elucidated. We examined the role of nitric oxide (NO) and its downstream effector guanylyl cyclase (CC) in mediating the effects of Gen on the proliferation and osteoblastic maturation of primary mouse bone marrow-derived mesenchymal stem cells (BMSCs). Gen (10 -8 ∼10 -6 M) resulted in a dose-dependent increase in cell proliferation as measured by increased [ 3 H]thymidine incorporation, and stimulated osteoblastic maturation as assessed by culture duration-dependent increments in alkaline phosphatase (ALP) activity, calcium deposition into extracellular matrix and Runx2/Cbfa1 gene expression in BMSCs cultures. Gen also resulted in a dose-dependent increase in NO synthase (NOS) activity, NO formation, and cGMP production in BMSCs cultures. The effects of Gen were mimicked by 17β-estradiol (E 2 , 10 -8 M). Concurrent treatment with the estrogen receptor (ER) antagonist ICI182,780 (10 -7 M) or the NOS inhibitor L-NAME (3 × 10 -3 M) diminished the Gen (10 -6 M)-mediated increase in NOS activity, NO production, and cGMP content. In contrast, a soluble GC inhibitor 1H-[1,2,4]oxadiazolo [4,3,-a]quinoxalin-1-one (ODQ, 10 -6 M) selectively blocked the Gen(10 -6 M)-mediated increase in cGMP content but not in NO production and NOS activity. Moreover, inhibition of ER, NOS activity or cGMP blocked Gen-induced proliferation and osteoblastic differentiation of BMSCs and Runx2/Cbfa1 gene expression in culture. Gen has estrogen-like activity and stimulates the proliferation and osteoblastic differentiation of mouse BMSCs at least in part through NO/cGMP pathway.",
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AU - Zhou, Hong Hao

AU - Xiao, Zhousheng

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