Role of Phytoestrogen Ferutinin in Preventing/Recovering Bone Loss: Results from Experimental Ovariectomized Rat Models

AbstractOsteocytes act as mechanosensors in bone; however, the underlying mechanism remains poorly understood. Here we report that deleting Kindlin-2 in osteocytes causes severe osteopenia and mechanical property defects in weight-bearing long bones, but not in non-weight-bearing calvariae. Kindlin-2 loss in osteocytes impairs skeletal responses to mechanical stimulation in long bones. Control and cKO mice display similar bone loss induced by unloading. However, unlike control mice, cKO mice fail to restore lost bone after reloading. Osteocyte Kindlin-2 deletion impairs focal adhesion (FA) formation, cytoskeleton organization and cell orientation in vitro and in bone. Fluid shear stress dose-dependently increases Kindlin-2 expression and decreases that of Sclerostin by downregulating Smad2/3 in osteocytes; this latter response is abolished by Kindlin-2 ablation. Kindlin-2-deficient osteocytes express abundant Sclerostin, contributing to bone loss in cKO mice. Collectively, we demonstrate an indispensable novel role of Kindlin-2 in maintaining skeletal responses to mechanical stimulation by inhibiting Sclerostin expression during osteocyte mechanotransduction.

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AT1 and AT2 Receptor Knockout Changed Osteonectin and Bone Density in Mice in Periodontal Inflammation Experimental Model

International Journal of Molecular Sciences ◽

10.3390/ijms22105217 ◽

2021 ◽

Vol 22 (10) ◽

pp. 5217

Author(s):

Maria Laura de Souza Lima ◽

Caroline Addison Carvalho Xavier de Medeiros ◽

Gerlane Coelho Bernardo Guerra ◽

Robson Santos ◽

Michael Bader ◽

...

Keyword(s):

Bone Density ◽

Bone Loss ◽

Experimental Model ◽

At2 Receptor ◽

Micro Ct ◽

Rt Pcr ◽

Osteoblast Cells ◽

Periodontal Inflammation ◽

Bone Trabeculae

Background: The aim of this study was to evaluate the role of AT1 and AT2 receptors in a periodontal inflammation experimental model. Methods: Periodontal inflammation was induced by LPS/Porphyromonas gingivalis. Maxillae, femur, and vertebra were scanned using Micro-CT. Maxillae were analyzed histopathologically, immunohistochemically, and by RT-PCR. Results: The vertebra showed decreased BMD in AT1 H compared with WT H (p < 0.05). The femur showed increased Tb.Sp for AT1 H and AT2 H, p < 0.01 and p < 0.05, respectively. The Tb.N was decreased in the vertebra (WT H-AT1 H: p < 0.05; WT H-AT2 H: p < 0.05) and in the femur (WT H-AT1 H: p < 0.01; WT H-AT2 H: p < 0.05). AT1 PD increased linear bone loss (p < 0.05) and decreased osteoblast cells (p < 0.05). RANKL immunostaining was intense for AT1 PD and WT PD (p < 0.001). OPG was intense in the WT H, WT PD, and AT2 PD when compared to AT1 PD (p < 0.001). AT1 PD showed weak immunostaining for osteocalcin compared with WT H, WT PD, and AT2 PD (p < 0.001). AT1 H showed significantly stronger immunostaining for osteonectin in fibroblasts compared to AT2 H (p < 0.01). Conclusion: AT1 receptor knockout changed bone density, the quality and number of bone trabeculae, decreased the number of osteoblast cells, and increased osteonectin in fibroblasts.

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The Dual Role of Vitamin K2 in “Bone-Vascular Crosstalk”: Opposite Effects on Bone Loss and Vascular Calcification

Nutrients ◽

10.3390/nu13041222 ◽

2021 ◽

Vol 13 (4) ◽

pp. 1222

Author(s):

Domitilla Mandatori ◽

Letizia Pelusi ◽

Valeria Schiavone ◽

Caterina Pipino ◽

Natalia Di Pietro ◽

...

Keyword(s):

Bone Loss ◽

Vascular Calcification ◽

Vascular System ◽

The Elderly ◽

Food Supplement ◽

Vitamin K2 ◽

Bioactive Molecules ◽

Calcium Deposition ◽

Age Related

Osteoporosis (OP) and vascular calcification (VC) represent relevant health problems that frequently coexist in the elderly population. Traditionally, they have been considered independent processes, and mainly age-related. However, an increasing number of studies have reported their possible direct correlation, commonly defined as “bone-vascular crosstalk”. Vitamin K2 (VitK2), a family of several natural isoforms also known as menaquinones (MK), has recently received particular attention for its role in maintaining calcium homeostasis. In particular, VitK2 deficiency seems to be responsible of the so-called “calcium paradox” phenomenon, characterized by low calcium deposition in the bone and its accumulation in the vessel wall. Since these events may have important clinical consequences, and the role of VitK2 in bone-vascular crosstalk has only partially been explained, this review focuses on its effects on the bone and vascular system by providing a more recent literature update. Overall, the findings reported here propose the VitK2 family as natural bioactive molecules that could be able to play an important role in the prevention of bone loss and vascular calcification, thus encouraging further in-depth studies to achieve its use as a dietary food supplement.

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Physiological plasma levels of androgens reduce bone loss in the ovariectomized rat

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1998.274.2.e328 ◽

1998 ◽

Vol 274 (2) ◽

pp. E328-E335 ◽

Cited By ~ 5

Author(s):

C. K. Lea ◽

A. M. Flanagan

Keyword(s):

Bone Resorption ◽

Bone Loss ◽

Protective Effect ◽

Cancellous Bone ◽

Plasma Levels ◽

Slow Release ◽

Bone Volume ◽

Ovariectomized Rat ◽

Ovx Rats ◽

Reduce Bone Loss

The effect of androstenedione (ADIONE) slow-release pellets on cancellous bone volume (BV/TV) at the tibial metaphysis was investigated in ovariectomized (OVX) rats at various times from 21 to 180 days. Plasma levels of ADIONE and testosterone (T) in OVX rats were significantly reduced at 21 days and were restored close to levels in the sham rats with the 1.5-mg ADIONE pellet. OVX animals with and without ADIONE pellets resulted in close to a 50% reduction in BV/TV by day 21. By day 180, OVX rats had only ∼5% BV/TV, whereas that in ADIONE-treated OVX rats was significantly greater at ∼12%. The reduced BV/TV was associated with increased bone resorption and formation. In a separate 90-day experiment, we found that the antiandrogen, Casodex, abrogated the ADIONE-induced skeletal-protective effect in OVX rats, whereas the antiaromatase, Arimidex, had no effect. This provides evidence that ADIONE protects against the development of osteopenia in the estrogen-deficient rat and mediates its effect through androgens and not estrogens.

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Role of endogenous regucalcin in bone metabolism: Bone loss is induced in regucalcin transgenic rats

International Journal of Molecular Medicine ◽

10.3892/ijmm.10.4.377 ◽

2002 ◽

Author(s):

Masayoshi Yamaguchi ◽

H. Misawa ◽

S. Uchiyama ◽

Y. Morooka ◽

Y. Tsurusaki

Keyword(s):

Bone Loss ◽

Bone Metabolism ◽

Transgenic Rats

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