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Genistein stimulates the osteoblastic differentiation via NO/cGMP in bone marrow culture
Author(s) -
Pan Wei,
Quarles L. Darryl,
Song LiHua,
Yu YanHui,
Jiao Chen,
Tang HongBo,
Jiang ChangHong,
Deng HanWu,
Li YuanJian,
Zhou HongHao,
Xiao ZhouSheng
Publication year - 2005
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.20308
Subject(s) - medicine , genistein , endocrinology , runx2 , chemistry , alkaline phosphatase , cell growth , cell culture , soluble guanylyl cyclase , estrogen receptor , nitric oxide , biology , biochemistry , enzyme , guanylate cyclase , genetics , cancer , breast cancer
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 (GC) 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 Runx 2/ Cbfa 1 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 Runx 2/ Cbfa 1 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. © 2004 Wiley‐Liss, Inc.