The BMP signaling pathway enhances the osteoblastic differentiation of bone marrow mesenchymal stem cells in rats with osteoporosis

Zhao, Bin; Xing, Gengyan; Wang, Aiyuan

doi:10.1186/s13018-019-1512-3

Cited by 15 publications

(12 citation statements)

References 26 publications

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“…The inhibition of prenylated proteins, which include RhoA and Rac1, led to the stimulation of bone morphogenetic proteins (BMP)-2 ( Hagihara et al, 2011 ; Onishi et al, 2013 ). The activation of BMP signaling pathways by BMP-2 could promote osteoblastic differentiation in osteoporotic rats ( Zhao et al, 2019 ). Moreover, in an in vitro study, annatto tocotrienol was demonstrated to activate the osteogenic activity of preosteoblastic MC3T3-E1 cell line via inhibition of RhoA and promotion of BMP-2 protein ( Wan Hasan et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Osteoprotective Effects in Postmenopausal Osteoporosis Rat Model: Oral Tocotrienol vs. Intraosseous Injection of Tocotrienol-Poly Lactic-Co-Glycolic Acid Combination

et al. 2021

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Osteoporosis, the most common bone disease, is associated with compromised bone strength and increased risk of fracture. Previous studies have shown that oxidative stress contributes to the progression of osteoporosis. Specifically, for postmenopausal osteoporosis, the reduction in estrogen levels leads to increased oxidative stress in bone remodeling. Tocotrienol, a member of vitamin E that exhibits antioxidant activities, has shown potential as an agent for the treatment of osteoporosis. Most studies on the osteoprotective effects of tocotrienols had used the oral form of tocotrienols, despite their low bioavailability due the lack of transfer proteins and high metabolism in the liver. Several bone studies have utilized tocotrienol combined with a nanocarrier to produce a controlled release of tocotrienol particles into the system. However, the potential of delivering tocotrienol–nanocarrier combination through the intraosseous route has never been explored. In this study, tocotrienol was combined with a nanocarrier, poly lactic-co-glycolic acid (PLGA), and injected intraosseously into the bones of ovariectomized rats to produce targeted and controlled delivery of tocotrienol into the bone microenvironment. This new form of tocotrienol delivery was compared with the conventional oral delivery in terms of their effects on bone parameters. Forty Sprague–Dawley rats were divided into five groups. The first group was sham operated, while other groups were ovariectomized (OVX). Following 2 months, the right tibiae of all the rats were drilled at the metaphysis region to provide access for intraosseous injection. The estrogen group (OVX + ESTO) and tocotrienol group (OVX + TTO) were given daily oral gavages of Premarin (64.5 mg/kg) and annatto-tocotrienol (60 mg/kg), respectively. The locally administered tocotrienol group (OVX + TTL) was given a single intraosseous injection of tocotrienol–PLGA combination. After 8 weeks of treatment, both OVX + TTO and OVX + TTL groups have significantly lower bone markers and higher bone mineral content than the OVX group. In terms of bone microarchitecture, both groups demonstrated significantly higher trabecular separation and connectivity density than the OVX group (p < 0.05). Both groups also showed improvement in bone strength by the significantly higher stress, strain, stiffness, and Young’s modulus parameters. In conclusion, daily oral tocotrienol and one-time intraosseous injection of tocotrienol–PLGA combination were equally effective in offering protection against ovariectomy-induced bone changes.

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Section: Discussionmentioning

confidence: 99%

Osteoprotective Effects in Postmenopausal Osteoporosis Rat Model: Oral Tocotrienol vs. Intraosseous Injection of Tocotrienol-Poly Lactic-Co-Glycolic Acid Combination

et al. 2021

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“…Moreover, in the absence of BMP-2, the Smad complexes remain bound and active on target genes [ 67 ]. The study conducted in osteoporosis rats showed that the overexpression of BMP-2 in rat bone marrow mesenchymal stem cells (rBMSCs) activates the BMP signaling pathway promoting osteoblastic differentiation, while the low expression of BMP-2 suppresses the BMP signaling pathway in rBMSCs [ 68 ]. The addition of BMP-2 in osteoporosis rats significantly improved bone repair and enhanced new bone formation in the margins of the defect as well as intramembranous ossification zones by reducing mineralization of the newly formed bone [ 69 ].…”

Section: Molecular Biology Of Osteoporosismentioning

confidence: 99%

The Development of Molecular Biology of Osteoporosis

Gao

Patil

Jia

2021

IJMS

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Osteoporosis is one of the major bone disorders that affects both women and men, and causes bone deterioration and bone strength. Bone remodeling maintains bone mass and mineral homeostasis through the balanced action of osteoblasts and osteoclasts, which are responsible for bone formation and bone resorption, respectively. The imbalance in bone remodeling is known to be the main cause of osteoporosis. The imbalance can be the result of the action of various molecules produced by one bone cell that acts on other bone cells and influence cell activity. The understanding of the effect of these molecules on bone can help identify new targets and therapeutics to prevent and treat bone disorders. In this article, we have focused on molecules that are produced by osteoblasts, osteocytes, and osteoclasts and their mechanism of action on these cells. We have also summarized the different pharmacological osteoporosis treatments that target different molecular aspects of these bone cells to minimize osteoporosis.

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“…Egr2 is a zinc finger transcription factor that has been demonstrated to be responsible for the negative regulation and inhibition of RANKL mediated osteoclast differentiation [ 25 , 27 ]. Data of several studies suggest the importance of RUNX2 transcription factor in regulating osteoporosis [ [28] , [29] , [30] ]. RUNX2, an osteogenesis-promoting transcription factor, promotes the proliferation of osteoblast progenitors and their commitment to osteoblasts lineage cells.…”

Section: Introductionmentioning

confidence: 99%

“…RUNX2, an osteogenesis-promoting transcription factor, promotes the proliferation of osteoblast progenitors and their commitment to osteoblasts lineage cells. An upregulation of RUNX2 thus suggests that some degree of osteogenesis had occurred in Saos-2 cells [ 30 ]. NFATc1 is considered to be a master transcription factor required for differentiation of osteoclasts.…”

Section: Introductionmentioning

confidence: 99%

Molecular insights for an anti-osteoporotic properties of Litsea glutinosa on Saos-2 cells: An in-vitro approach

Changani

Parikh

2022

Journal of Ayurveda and Integrative Medicine

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Osteoporosis is a skeletal disease that is identified by the deterioration of micro-architecture of bone tissue, leading to enhanced bone brittleness and a consequential increase in fracture threat. There are many treatments available for osteoporosis such as bisphosphonate therapy, hormonal replacement therapy, herbal therapy etc. For decades, there are several herbs that are attributed to have anti-osteoporotic effects however the candidate genes involved in it remained unknown. In line with this, the present study is focused to elucidate the anti-osteoporotic property of Litsea glutinosa (LG). To understand the proliferative effect and identify involved players, gene expression was studied on the Saos-2 osteocytes in-vitro . The expression profile of candidate genes involved in different signaling pathways such as Egr-2, RUNX2, MAPK3, NFATc1, CREB, ERβ, along with proliferation and apoptotic markers in osteoporosis were selected for the study. The gene expression profile demonstrated a significant up-regulation of Egr-2, RUNX2, MAPK3, CREB, EBβ in the range of 1.5–2.2 folds, whereas NFATc1 was found to be down-regulated up to 0.4 times compared to control when treated with 250 μg/mL of LG. Besides this, anti-apoptosis effect of LG was also supported by flow cytometry results which also proved that LG induces proliferation and inhibits apoptosis, suggesting the proliferative role of LG. In conclusion, the present study gathers the potency of LG extract for its proliferative and anti-apoptotic effect on Saos-2 osteocytes and opens a new avenue for detailing the mechanistic actions of it on mitigating the pathophysiology of osteoporosis.

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The BMP signaling pathway enhances the osteoblastic differentiation of bone marrow mesenchymal stem cells in rats with osteoporosis

Cited by 15 publications

References 26 publications

Osteoprotective Effects in Postmenopausal Osteoporosis Rat Model: Oral Tocotrienol vs. Intraosseous Injection of Tocotrienol-Poly Lactic-Co-Glycolic Acid Combination

Osteoprotective Effects in Postmenopausal Osteoporosis Rat Model: Oral Tocotrienol vs. Intraosseous Injection of Tocotrienol-Poly Lactic-Co-Glycolic Acid Combination

The Development of Molecular Biology of Osteoporosis

Molecular insights for an anti-osteoporotic properties of Litsea glutinosa on Saos-2 cells: An in-vitro approach

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