Differential effects of formononetin and cladrin on osteoblast function, peak bone mass achievement and bioavailability in rats

Type 2 diabetes is associated with increased fracture risk and delayed facture healing; the underlying mechanism, however, remains poorly understood. We systematically investigated skeletal pathology in leptin receptor–deficient diabetic mice on a C57BLKS background (db). Compared with wild type (wt), db mice displayed reduced peak bone mass and age-related trabecular and cortical bone loss. Poor skeletal outcome in db mice contributed high-glucose– and nonesterified fatty acid–induced osteoblast apoptosis that was associated with peroxisome proliferator–activated receptor γ coactivator 1-α (PGC-1α) downregulation and upregulation of skeletal muscle atrogenes in osteoblasts. Osteoblast depletion of the atrogene muscle ring finger protein-1 (MuRF1) protected against gluco- and lipotoxicity-induced apoptosis. Osteoblast-specific PGC-1α upregulation by 6-C-β-d-glucopyranosyl-(2S,3S)-(+)-5,7,3′,4′-tetrahydroxydihydroflavonol (GTDF), an adiponectin receptor 1 (AdipoR1) agonist, as well as metformin in db mice that lacked AdipoR1 expression in muscle but not bone restored osteopenia to wt levels without improving diabetes. Both GTDF and metformin protected against gluco- and lipotoxicity-induced osteoblast apoptosis, and depletion of PGC-1α abolished this protection. Although AdipoR1 but not AdipoR2 depletion abolished protection by GTDF, metformin action was not blocked by AdipoR depletion. We conclude that PGC-1α upregulation in osteoblasts could reverse type 2 diabetes–associated deterioration in skeletal health.

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“…Three-point bending test on femur was performed using a bone strength tester (TK-252C; Muromachi) as previously reported (29).…”

Section: Bone Biomechanical Strengthmentioning

confidence: 99%

Pathophysiological Mechanism of Bone Loss in Type 2 Diabetes Involves Inverse Regulation of Osteoblast Function by PGC-1α and Skeletal Muscle Atrogenes: AdipoR1 as a Potential Target for Reversing Diabetes-Induced Osteopenia

et al. 2015

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“…Dynamic histomorphometric parameters calculated from the labeling experiments showing increased MAR (b, c) and BFR (d, e) at the periosteal and endosteal sites. N=10 rats/group; data represented as mean ± SEM; **P<0.01 and ***P<0.001 compared to vehicle-treated group (control) reported to promote peak bone mass achievement, but their effects in inducing new bone formation in osteopenic condition has not been investigated [37,54]. Here, we used osteopenic rats that had been OVx 13 weeks prior to the start of the QCG treatment to test if it reversed osteopenia.…”

Section: Discussionmentioning

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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“…Mouse calvarial osteoblasts were obtained following our previously published protocol of sequential digestion (Gautam et al, 2011;Lin et al, 2003). Calvariae were subjected to five sequential digestions at 37 1C in 0.1% dispase and 0.1% collagenase P solution.…”

Section: In Vitro Bone Formation Using Osteoblast Culturementioning

confidence: 99%

Potential osteogenic activity of ethanolic extract and oxoflavidin isolated from Pholidota articulata Lindley

Sharma

Dixit

Singh

et al. 2015

Journal of Ethnopharmacology

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Differential effects of formononetin and cladrin on osteoblast function, peak bone mass achievement and bioavailability in rats

Cited by 74 publications

References 52 publications

Pathophysiological Mechanism of Bone Loss in Type 2 Diabetes Involves Inverse Regulation of Osteoblast Function by PGC-1α and Skeletal Muscle Atrogenes: AdipoR1 as a Potential Target for Reversing Diabetes-Induced Osteopenia

Pathophysiological Mechanism of Bone Loss in Type 2 Diabetes Involves Inverse Regulation of Osteoblast Function by PGC-1α and Skeletal Muscle Atrogenes: AdipoR1 as a Potential Target for Reversing Diabetes-Induced Osteopenia

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

Potential osteogenic activity of ethanolic extract and oxoflavidin isolated from Pholidota articulata Lindley

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