Medicarpin inhibits osteoclastogenesis and has nonestrogenic bone conserving effect in ovariectomized mice

Tyagi, Abdul Malik; Gautam, Anurag; Kumar, Amit; Srivastava, Kirti; Bhargavan, Biju; Trivedi, Ritu; Saravanan, S.; Yadav, Deepti; Singh, Nidhi; Pollet, Caroline; Brazier, Michel; Mentaverri, Romuald; Maurya, Rakesh; Chattopadhyay, Naibedya; Goel, Atul; Singh, Divya

doi:10.1016/j.mce.2010.05.016

Cited by 62 publications

(55 citation statements)

References 48 publications

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“…Osteoclast Culture and TRAP Staining and siRNA Transfection-In vitro osteoclastogenesis was carried out using a standard protocol (37). Bone marrow was isolated from 8-to 9-week-old female BALB/c mice by flushing bones with ␣-MEM.…”

Section: Methodsmentioning

confidence: 99%

Interleukin 27 (IL-27) Alleviates Bone Loss in Estrogen-deficient Conditions by Induction of Early Growth Response-2 Gene

Shukla

Mansoori

Kakaji

et al. 2017

Journal of Biological Chemistry

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Edited by Xiao-Fan WangA growing understanding of the bone remodeling process suggests that inflammation significantly contributes to the pathogenesis of osteoporosis. T cells and various cytokines contribute majorly to the estrogen deficiency-induced bone loss. Recent studies have identified the IL-12 cytokine family as consisting of pro-inflammatory IL-12 and IL-23 and the anti-inflammatory IL-27 and IL-35 cytokines. IL-27 exerts protective effects in autoimmune diseases like experimental autoimmune encephalomyelitis; however, its role in the pathogenesis of osteoporosis remains to be determined. In this report, we study the effect of IL-27 supplementation on ovariectomized estrogen-deficient mice on various immune and skeletal parameters. IL-27 treatment in ovariectomized mice suppressed Th17 cell differentiation by inhibiting transcription factor ROR␥t. Supplementation of IL-27 activates Egr-2 to induce IL-10 producing Tr1 cells. IL-27 treatment prevented the loss of trabecular micro-architecture and preservedcorticalboneparameters.IL-27alsoinhibitedosteoblastapo-ptosis through increased Egr-2 expression, which induces antiapoptotic factors like MCL-1. IL-27 suppressed osteoclastogenesis in an Egr-2-dependent manner that up-regulates Id2, the repressor of the receptor activator of nuclear factor-B ligand-mediated osteoclastogenesis. Additionally, these results were corroborated in female osteoporotic subjects where we found decreased serum IL-27 levels along with reduced Egr-2 expression. Our study forms a strong basis for using humanized IL-27 toward the treatment of post-menopausal osteoporosis.

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Section: Methodsmentioning

confidence: 99%

Interleukin 27 (IL-27) Alleviates Bone Loss in Estrogen-deficient Conditions by Induction of Early Growth Response-2 Gene

Shukla

Mansoori

Kakaji

et al. 2017

Journal of Biological Chemistry

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“…Recently, we have shown bone conserving effect of medicarpin (Med), a pterocarpantype phytoalexin present in dietary legume, in Ovx mice, suggesting its E2-"like" effect on bone. Med was devoid of any uterotrophic effect [21]. In this study, we aim to determine the effect of estrogen deficiency on CD28 expression on T cells and the role of E2/Med in this phenomenon.…”

Section: Introductionmentioning

confidence: 99%

Premature T cell senescence in Ovx mice is inhibited by repletion of estrogen and medicarpin: a possible mechanism for alleviating bone loss

et al. 2011

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To our knowledge this is the first report to determine the mechanism of CD28 loss on T cells as a result of ovariectomy. Our study demonstrates that Ovx leads to the generation of premature senescent CD4(+)CD28null T cells, an effect inhibited by E2 and Med. We propose that one of the mechanisms by which Med/E2 alleviates Ovx-induced bone loss is by delaying T cell senescence and enhancing CD28 expression.

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“…RCO were pre-treated with ICI-182780 for 30 min prior to QCG treatment, and ALP production was determined as described above [39].…”

Section: Alp Assaymentioning

confidence: 99%

A naturally occurring rare analog of quercetin promotes peak bone mass achievement and exerts anabolic effect on osteoporotic bone

et al. 2011

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Medicarpin inhibits osteoclastogenesis and has nonestrogenic bone conserving effect in ovariectomized mice

Cited by 62 publications

References 48 publications

Interleukin 27 (IL-27) Alleviates Bone Loss in Estrogen-deficient Conditions by Induction of Early Growth Response-2 Gene

Interleukin 27 (IL-27) Alleviates Bone Loss in Estrogen-deficient Conditions by Induction of Early Growth Response-2 Gene

Premature T cell senescence in Ovx mice is inhibited by repletion of estrogen and medicarpin: a possible mechanism for alleviating bone loss

A naturally occurring rare analog of quercetin promotes peak bone mass achievement and exerts anabolic effect on osteoporotic bone

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