TY - JOUR
T1 - 8,8″-Biapigeninyl stimulates osteoblast functions and inhibits osteoclast and adipocyte functions
T2 - Osteoprotective action of 8,8″-biapigeninyl in ovariectomized mice
AU - Siddiqui, Jawed A.
AU - Swarnkar, Gaurav
AU - Sharan, Kunal
AU - Chakravarti, Bandana
AU - Sharma, Gunjan
AU - Rawat, Preeti
AU - Kumar, Manmeet
AU - Khan, Faheem M.
AU - Pierroz, Dominique
AU - Maurya, Rakesh
AU - Chattopadhyay, Naibedya
N1 - Funding Information:
Supporting grants: This study was supported by the Ministry of Heath and Family Welfare, Council of Scientific and Industrial Research, and the University Grants Commission, Government of India. Funding from Department of Biotechnology, Government of India to N.C. is acknowledged. Fellowship grants were given by the University Grant Commission, Government of India (to J.A.S.), Department of Biotechnology, Government of India (to K.S.), and Council of Scientific and Industrial Research, Government of India (to G.S., B.C., P.R., M.K.).
PY - 2010/7
Y1 - 2010/7
N2 - 8,8″-Biapigeninyl (BA), a condensation product of two apigenin molecules, is found abundantly in the nuts of Cupressus sempervirens. We investigated the effects of BA on murine bone cells in vitro and in ovariectomized (OVx) mice. BA at 10-10M and 10-8M, inhibited osteoclastogenesis of bone marrow cells (BMCs) and displayed concentration dependence. BA at 10-8M and 10-6M inhibited differentiation of 3T3-L1 and BMCs to mature adipocytes. BA (10-10M) stimulated osteoblast proliferation, differentiation and mineralization. In stimulating osteoblast function, BA was found to be 104-fold more potent than apigenin. The effect of BA in osteoblasts appeared to be mediated via estrogen receptors (ER) as antiestrogen, ICI-182780 abolished BA-stimulated osteoblast differentiation. In OVx mice BA treatment (at 1.0-, 5.0- and 10.0mgkg-1day-1 doses) given orally for 30 days dose-dependently inhibited mRNA levels of osteoclastic genes including tartrate-resistant acid phosphatase, receptor activator of nuclear factor (RANK), tumor necrosis factor alpha, interleukin-6 and the ratio of RANK ligand/osteoprotegerin ratio in bones compared with OVx mice treated with vehicle. In addition, BA treatment to OVx mice dose-dependently stimulated production of osteoprogenitor cells in the bone marrow and increased mRNA levels of osteogenic genes core binding factor alpha-1, type I collagen and bone morphogenic protein-2 in bones compared with OVx+vehicle group. Microcomputed tomography revealed that BA treatment to OVx mice improved parameters of trabecular and cortical architecture. BA exhibited no uterine estrogenicity. From these data, we conclude that BA exerts osteoprotective effect in OVx mice by multiple beneficial effects on bone cells.
AB - 8,8″-Biapigeninyl (BA), a condensation product of two apigenin molecules, is found abundantly in the nuts of Cupressus sempervirens. We investigated the effects of BA on murine bone cells in vitro and in ovariectomized (OVx) mice. BA at 10-10M and 10-8M, inhibited osteoclastogenesis of bone marrow cells (BMCs) and displayed concentration dependence. BA at 10-8M and 10-6M inhibited differentiation of 3T3-L1 and BMCs to mature adipocytes. BA (10-10M) stimulated osteoblast proliferation, differentiation and mineralization. In stimulating osteoblast function, BA was found to be 104-fold more potent than apigenin. The effect of BA in osteoblasts appeared to be mediated via estrogen receptors (ER) as antiestrogen, ICI-182780 abolished BA-stimulated osteoblast differentiation. In OVx mice BA treatment (at 1.0-, 5.0- and 10.0mgkg-1day-1 doses) given orally for 30 days dose-dependently inhibited mRNA levels of osteoclastic genes including tartrate-resistant acid phosphatase, receptor activator of nuclear factor (RANK), tumor necrosis factor alpha, interleukin-6 and the ratio of RANK ligand/osteoprotegerin ratio in bones compared with OVx mice treated with vehicle. In addition, BA treatment to OVx mice dose-dependently stimulated production of osteoprogenitor cells in the bone marrow and increased mRNA levels of osteogenic genes core binding factor alpha-1, type I collagen and bone morphogenic protein-2 in bones compared with OVx+vehicle group. Microcomputed tomography revealed that BA treatment to OVx mice improved parameters of trabecular and cortical architecture. BA exhibited no uterine estrogenicity. From these data, we conclude that BA exerts osteoprotective effect in OVx mice by multiple beneficial effects on bone cells.
KW - Adipogenesis
KW - Biflavone
KW - Bone microarchitecture
KW - Estrogenicity
KW - Osteogenic
UR - http://www.scopus.com/inward/record.url?scp=77952954226&partnerID=8YFLogxK
U2 - 10.1016/j.mce.2010.03.024
DO - 10.1016/j.mce.2010.03.024
M3 - Article
C2 - 20380869
AN - SCOPUS:77952954226
SN - 0303-7207
VL - 323
SP - 256
EP - 267
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
IS - 2
ER -