A novel flavonoid C-glucoside from Ulmus wallichiana preserves bone mineral density, microarchitecture and biomechanical properties in the presence of glucocorticoid by promoting osteoblast survival

A comparative study with human parathyroid hormone

M. P. Khan, J. S. Mishra, K. Sharan, M. Yadav, A. K. Singh, A. Srivastava, S. Kumar, S. Bhaduaria, R. Maurya, S. Sanyal, N. Chattopadhyay

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Purpose 6-C-β-d-glucopyranosyl-(2S,3S)-(+)-5,7,3′,4′- tetrahydroxydihydroflavonol (GTDF) is a novel compound isolated from Ulmus wallichiana, reported to have bone anabolic action in ovariectomized rats. Here, we studied the effect of GTDF in glucocorticoid (GC)-induced bone loss and its mode of action. Methods Osteoblasts were cultured from rat calvaria or bone marrow to study apoptosis and differentiation by dexamethasone (Dex), methylprednisolone (MP), GTDF, quercetin and rutin. Female Sprague Dawley rats were treated with Dex or MP with or without GTDF or PTH. Efficacy was evaluated by bone microarchitecture using microcomputed tomography, determination of new bone formation by fluorescent labeling of bone and osteoblast apoptosis by co-labeling bone sections with Runx-2 and TUNEL. Serum osteocalcin was determined by ELISA. Results GTDF preserved trabecular and cortical bones in the presence of Dex and MP and mitigated the MP-mediated suppression of serum osteocalcin. Co-administration of GTDF to MP rats increased mineral apposition, bone formation rates, bone biomechanical strength, reduced osteoblast apoptosis and increased osteogenic differentiation of bone marrow stromal cells compared to MP group, suggesting in vivo osteogenic effect of GTDF. These effects of GTDF were to a great extent comparable to PTH. GTDF prevented GC-induced osteoblast apoptosis by inhibiting p53 expression and acetylation, and activation of AKT but did not influence transactivation of GC receptor (GR). Conclusions GTDF protects against GC-induced bone loss by promoting osteoblast survival through p53 inhibition and activation of AKT pathways but not as a GR antagonist. GTDF has the potential in the management of GC-induced osteopenia.

Original languageEnglish (US)
Pages (from-to)1256-1266
Number of pages11
JournalPhytomedicine
Volume20
Issue number14
DOIs
StatePublished - Nov 15 2013
Externally publishedYes

Fingerprint

Ulmus
Glucosides
Osteoblasts
Flavonoids
Methylprednisolone
Bone Density
Glucocorticoids
Bone and Bones
Apoptosis
Dexamethasone
Osteocalcin
Osteogenesis
X-Ray Microtomography
Rutin
Metabolic Bone Diseases
Quercetin
Glucocorticoid Receptors
In Situ Nick-End Labeling
Acetylation
human PTH protein

Keywords

  • AKT pathway
  • Bone anabolic
  • Bone histomorphometry
  • Glucocorticoid-induced osteoporosis
  • Quercetin
  • Runx-2

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Pharmaceutical Science
  • Complementary and alternative medicine
  • Molecular Medicine

Cite this

A novel flavonoid C-glucoside from Ulmus wallichiana preserves bone mineral density, microarchitecture and biomechanical properties in the presence of glucocorticoid by promoting osteoblast survival : A comparative study with human parathyroid hormone. / Khan, M. P.; Mishra, J. S.; Sharan, K.; Yadav, M.; Singh, A. K.; Srivastava, A.; Kumar, S.; Bhaduaria, S.; Maurya, R.; Sanyal, S.; Chattopadhyay, N.

In: Phytomedicine, Vol. 20, No. 14, 15.11.2013, p. 1256-1266.

Research output: Contribution to journalArticle

Khan, M. P. ; Mishra, J. S. ; Sharan, K. ; Yadav, M. ; Singh, A. K. ; Srivastava, A. ; Kumar, S. ; Bhaduaria, S. ; Maurya, R. ; Sanyal, S. ; Chattopadhyay, N. / A novel flavonoid C-glucoside from Ulmus wallichiana preserves bone mineral density, microarchitecture and biomechanical properties in the presence of glucocorticoid by promoting osteoblast survival : A comparative study with human parathyroid hormone. In: Phytomedicine. 2013 ; Vol. 20, No. 14. pp. 1256-1266.
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abstract = "Purpose 6-C-β-d-glucopyranosyl-(2S,3S)-(+)-5,7,3′,4′- tetrahydroxydihydroflavonol (GTDF) is a novel compound isolated from Ulmus wallichiana, reported to have bone anabolic action in ovariectomized rats. Here, we studied the effect of GTDF in glucocorticoid (GC)-induced bone loss and its mode of action. Methods Osteoblasts were cultured from rat calvaria or bone marrow to study apoptosis and differentiation by dexamethasone (Dex), methylprednisolone (MP), GTDF, quercetin and rutin. Female Sprague Dawley rats were treated with Dex or MP with or without GTDF or PTH. Efficacy was evaluated by bone microarchitecture using microcomputed tomography, determination of new bone formation by fluorescent labeling of bone and osteoblast apoptosis by co-labeling bone sections with Runx-2 and TUNEL. Serum osteocalcin was determined by ELISA. Results GTDF preserved trabecular and cortical bones in the presence of Dex and MP and mitigated the MP-mediated suppression of serum osteocalcin. Co-administration of GTDF to MP rats increased mineral apposition, bone formation rates, bone biomechanical strength, reduced osteoblast apoptosis and increased osteogenic differentiation of bone marrow stromal cells compared to MP group, suggesting in vivo osteogenic effect of GTDF. These effects of GTDF were to a great extent comparable to PTH. GTDF prevented GC-induced osteoblast apoptosis by inhibiting p53 expression and acetylation, and activation of AKT but did not influence transactivation of GC receptor (GR). Conclusions GTDF protects against GC-induced bone loss by promoting osteoblast survival through p53 inhibition and activation of AKT pathways but not as a GR antagonist. GTDF has the potential in the management of GC-induced osteopenia.",
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T1 - A novel flavonoid C-glucoside from Ulmus wallichiana preserves bone mineral density, microarchitecture and biomechanical properties in the presence of glucocorticoid by promoting osteoblast survival

T2 - A comparative study with human parathyroid hormone

AU - Khan, M. P.

AU - Mishra, J. S.

AU - Sharan, K.

AU - Yadav, M.

AU - Singh, A. K.

AU - Srivastava, A.

AU - Kumar, S.

AU - Bhaduaria, S.

AU - Maurya, R.

AU - Sanyal, S.

AU - Chattopadhyay, N.

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N2 - Purpose 6-C-β-d-glucopyranosyl-(2S,3S)-(+)-5,7,3′,4′- tetrahydroxydihydroflavonol (GTDF) is a novel compound isolated from Ulmus wallichiana, reported to have bone anabolic action in ovariectomized rats. Here, we studied the effect of GTDF in glucocorticoid (GC)-induced bone loss and its mode of action. Methods Osteoblasts were cultured from rat calvaria or bone marrow to study apoptosis and differentiation by dexamethasone (Dex), methylprednisolone (MP), GTDF, quercetin and rutin. Female Sprague Dawley rats were treated with Dex or MP with or without GTDF or PTH. Efficacy was evaluated by bone microarchitecture using microcomputed tomography, determination of new bone formation by fluorescent labeling of bone and osteoblast apoptosis by co-labeling bone sections with Runx-2 and TUNEL. Serum osteocalcin was determined by ELISA. Results GTDF preserved trabecular and cortical bones in the presence of Dex and MP and mitigated the MP-mediated suppression of serum osteocalcin. Co-administration of GTDF to MP rats increased mineral apposition, bone formation rates, bone biomechanical strength, reduced osteoblast apoptosis and increased osteogenic differentiation of bone marrow stromal cells compared to MP group, suggesting in vivo osteogenic effect of GTDF. These effects of GTDF were to a great extent comparable to PTH. GTDF prevented GC-induced osteoblast apoptosis by inhibiting p53 expression and acetylation, and activation of AKT but did not influence transactivation of GC receptor (GR). Conclusions GTDF protects against GC-induced bone loss by promoting osteoblast survival through p53 inhibition and activation of AKT pathways but not as a GR antagonist. GTDF has the potential in the management of GC-induced osteopenia.

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KW - AKT pathway

KW - Bone anabolic

KW - Bone histomorphometry

KW - Glucocorticoid-induced osteoporosis

KW - Quercetin

KW - Runx-2

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