A novel quercetin analogue from a medicinal plant promotes peak bone mass achievement and bone healing after injury and exerts an anabolic effect on osteoporotic bone: The role of aryl hydrocarbon receptor as a mediator of osteogenic action

Kunal Sharan, Jay Sharan Mishra, Gaurav Swarnkar, Jawed Akhtar Siddiqui, Kainat Khan, Rashmi Kumari, Preeti Rawat, Rakesh Maurya, Sabyasachi Sanyal, Naibedya Chattopadhyay

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

We recently reported that extracts made from the stem bark of Ulmus wallichiana promoted peak bone mass achievement in growing rats and preserved trabecular bone mass and cortical bone strength in ovariectomized (OVX) rats. Further, 6-C-β-D-glucopyranosyl-(2S,3S)-(+)-3',4',5,7-tetrahydroxyflavanol (GTDF), a novel flavonol-C-glucoside isolated from the extracts, had a nonestrogenic bone-sparing effect on OVX rats. Here we studied the effects of GTDF on osteoblast function and its mode of action and in vivo osteogenic effect. GTDF stimulated osteoblast proliferation, survival, and differentiation but had no effect on osteoclastic or adipocytic differentiation. In cultured osteoblasts, GTDF transactivated the aryl hydrocarbon receptor (AhR). Activation of AhR mediated the stimulatory effect of GTDF on osteoblast proliferation and differentiation. Furthermore, GTDF stimulated cAMP production, which mediated osteogenic gene expression. GTDF treatments given to 1- to 2-day-old rats or adult rats increased the mRNA levels of AhR target genes in calvaria or bone marrow stromal cells. In growing female rats, GTDF promoted parameters of peak bone accrual in the appendicular skeleton, including increased longitudinal growth, bone mineral density, bone-formation rate (BFR), cortical deposition, and bone strength. GTDF promoted the process of providing newly generated bone to fill drill holes in the femurs of both estrogen-sufficient and -deficient rats. In osteopenic OVX rats, GTDF increased BFR and significantly restored trabecular bone compared with the ovaries-intact group. Together our data suggest that GTDF stimulates osteoblast growth and differentiation via the AhR and promotes modeling-directed bone accrual, accelerates bone healing after injury, and exerts anabolic effects on osteopenic rats likely by a direct stimulatory effect on osteoprogenitors. Based on these preclinical data, clinical evaluation of GTDF as a potential bone anabolic agent is warranted.

Original languageEnglish (US)
Pages (from-to)2096-2111
Number of pages16
JournalJournal of Bone and Mineral Research
Volume26
Issue number9
DOIs
StatePublished - Sep 2011
Externally publishedYes

Fingerprint

Anabolic Agents
Aryl Hydrocarbon Receptors
Quercetin
Medicinal Plants
Bone and Bones
Osteoblasts
Wounds and Injuries
Osteogenesis
Ulmus
Glucosides
Growth
Mesenchymal Stromal Cells
Skull
Skeleton
Bone Density
Femur
Ovary
Estrogens
Gene Expression
Messenger RNA

Keywords

  • BONE HISTOMORPHOMETRY
  • MENOPAUSE
  • NOVEL ENTITIES
  • OSTEOBLASTS
  • OSTEOPOROSIS

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

A novel quercetin analogue from a medicinal plant promotes peak bone mass achievement and bone healing after injury and exerts an anabolic effect on osteoporotic bone : The role of aryl hydrocarbon receptor as a mediator of osteogenic action. / Sharan, Kunal; Mishra, Jay Sharan; Swarnkar, Gaurav; Siddiqui, Jawed Akhtar; Khan, Kainat; Kumari, Rashmi; Rawat, Preeti; Maurya, Rakesh; Sanyal, Sabyasachi; Chattopadhyay, Naibedya.

In: Journal of Bone and Mineral Research, Vol. 26, No. 9, 09.2011, p. 2096-2111.

Research output: Contribution to journalArticle

Sharan, Kunal ; Mishra, Jay Sharan ; Swarnkar, Gaurav ; Siddiqui, Jawed Akhtar ; Khan, Kainat ; Kumari, Rashmi ; Rawat, Preeti ; Maurya, Rakesh ; Sanyal, Sabyasachi ; Chattopadhyay, Naibedya. / A novel quercetin analogue from a medicinal plant promotes peak bone mass achievement and bone healing after injury and exerts an anabolic effect on osteoporotic bone : The role of aryl hydrocarbon receptor as a mediator of osteogenic action. In: Journal of Bone and Mineral Research. 2011 ; Vol. 26, No. 9. pp. 2096-2111.
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