RETRACTED: Effect of resveratrol and mesenchymal stem cell monotherapy and combined treatment in management of osteoporosis in ovariectomized rats: Role of SIRT1/FOXO3a and Wnt/β-catenin pathways

Elseweidy, Mohamed M.; Elswefy, Sahar E; Shaheen, Mohamed A.; Baraka, Nourhan M.; Hammad, Sally K

doi:10.1016/j.abb.2021.108856

“…Hong et al [20] found that hUCB-MSCs could enhance bone regeneration in a rat model of osteoporosis. Elseweidy et al [26] demonstrated that the combination of MSC and the antioxidant resveratrol was more effective in increasing bone mass and improving osteoporosis than treatment alone. Some studies had shown that the combination of plateletrich fibrin releasates (PRFr) and BMSCs [27] or ADSCs 10 Stem Cells International [28] could reduce bone loss in OVX osteoporotic mice.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Efficacy of Stem Cell Therapy in Ovariectomized Osteoporotic Rats Based on Micro-CT and Dual-Energy X-Ray Absorptiometry: A Systematic Review and Meta-Analysis

Xiong

¹

,

Yi

²

,

Lin

³

et al. 2021

Stem Cells International

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Objective. Osteoporosis is an abnormal bone metabolism disease characterized by microstructural degeneration of bone tissue and reduction in bone mass, resulting in increased brittleness of bone tissue and susceptibility to fracture. Due to the tissue regenerative potential of stem cell transplantation, it is now used in the treatment of various disease models such as osteoporosis. The purpose of this work is to carry out a systematic review and meta-analysis of the efficacy of stem cell therapy in ovariectomized (OVX) osteoporotic rats. Methods. PubMed, Cochrane Library, ScienceDirect, Embase, CNKI, and Wanfang Databases were used to search for articles that met the inclusion criteria. Two researchers independently screened the articles that met the inclusion criteria. RevMan 5.3 and STATA 16.0 were used for data analysis. This meta-analysis was registered at INPLASY with reference number ID: INPLASY202150017. Results. Thirteen eligible studies were selected, including 405 rats. The sources of stem cells are divided into four main categories: bone marrow mesenchymal stem cells (BMSCs), adipose-derived stem cells (ADSCs), amniotic membrane mesenchymal stem cells (AM-MSCs), and human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs). Compared with the OVX group, both stem cell transplantation groups had higher bone mineral density (BMD) (BMSCs: SMD = 2.01 , 95% CI: [1.38, 2.63], P < 0.001 , I 2 = 76.6 % ; ADSCs: SMD = 2.24 , 95% CI: [0.79, 3.69], P = 0.003 , I 2 = 86.7 % ) and bone volume/total volume (BV/TV) (hUCB-MSCs: SMD = 1.71 , 95% CI: [0.97, 2.44], P < 0.001 , I 2 = 0 % ; ADSCs: SMD = 2.16 , 95% CI: [0.27, 4.04], P = 0.025 , I 2 = 82.6 % ). In the BMSC treatment groups, the trabecular numbers (Tb.N) ( SMD = 4.28 , 95% CI: [0.91, 7.64], P = 0.013 , I 2 = 94.9 % ) were significantly higher, whereas the results for trabecular thickness (Tb.Th) ( SMD = 2.7 , 95% CI: [-0.34, 5.73], P = 0.081 , I 2 = 95.4 % ) and trabecular spacing (Tb.Sp) ( SMD = − 3.08 , 95% CI: [-6.55, 0.38], P = 0.081 , I 2 = 96.3 % ) were not statistically significant compared to those of the OVX group. The stem cell transplantation group had a low BMD, BV/TV, and Tb.N compared to the sham operation group. Conclusion. Stem cell therapy may increase bone strength, bone volume, and the number of trabeculae in OVX osteoporotic rats. The results of this meta-analysis showed the potential therapeutic effect of stem cell transplantation in OVX osteoporotic rats, bringing new therapeutic ideas and directions to the clinical treatment of osteoporosis. Due to the limited number and quality of studies related to some outcomes, more high-quality RCTs are still needed in the future to complement the existing findings.

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“…Besides such effects, it also exerts favorable effects on osteoporosis in ovariectomized rats and mice, as summarized in Table 1 . Several studies have demonstrated that the oral administration of resveratrol in ovariectomized rodents mitigates estrogen deficiency-induced bone loss [ 22 , 23 , 24 , 25 , 26 , 27 , 28 ], and with respect to its anti-osteoporotic mechanisms, it has been demonstrated that resveratrol not only promotes osteoblast differentiation but also suppresses osteoclast differentiation [ 22 , 24 , 28 ]. It has been proposed that microRNAs (miRNAs/miRs) play a pivotal role in estrogen deficiency-induced osteoporosis prevention.…”

Section: Resveratrolmentioning

confidence: 99%

“…Orally administered resveratrol increases osteoblast differentiation in ovariectomized rats via the activation of SIRT1 and the subsequent suppression of NF-κB activity [ 22 ]. It has also been reported that the management of osteoporosis in resveratrol-treated ovariectomized rats could be achieved by activating two signaling pathways—namely, the SIRT1 and wingless-related MMTV integration site (Wnt) pathways [ 28 ]. The receptor activator of NF-κB ligand (RANKL), which is released by osteoblasts and is essential for osteoclast development and activation, and its receptor, RANK, signal the activation of NF-κB, resulting in accelerated osteoclast differentiation [ 30 , 31 , 32 ].…”

Section: Resveratrolmentioning

confidence: 99%

“…The receptor activator of NF-κB ligand (RANKL), which is released by osteoblasts and is essential for osteoclast development and activation, and its receptor, RANK, signal the activation of NF-κB, resulting in accelerated osteoclast differentiation [ 30 , 31 , 32 ]. However, the activation of SIRT1 by resveratrol can suppress RANKL-induced NF-κB activity [ 22 , 28 ]. The Wnt signaling pathway not only promotes osteoblast proliferation but also attenuates their apoptosis [ 33 ], and this is further enhanced by SIRT1 [ 34 , 35 ].…”

Section: Resveratrolmentioning

confidence: 99%

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Anti-Osteoporotic Mechanisms of Polyphenols Elucidated Based on In Vivo Studies Using Ovariectomized Animals

Niwano

¹

,

Kohzaki

²

,

Shirato

³

et al. 2022

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Polyphenols are widely known for their antioxidant activity, i.e., they have the ability to suppress oxidative stress, and this behavior is mediated by the autoxidation of their phenolic hydroxyl groups. Postmenopausal osteoporosis is a common health problem that is associated with estrogen deficiency. Since oxidative stress is thought to play a key role in the onset and progression of osteoporosis, it is expected that polyphenols can serve as a safe and suitable treatment in this regard. Therefore, in this review, we aimed to elucidate the anti-osteoporotic mechanisms of polyphenols reported by in vivo studies involving the use of ovariectomized animals. We categorized the polyphenols as resveratrol, purified polyphenols other than resveratrol, or polyphenol-rich substances or extracts. Literature data indicated that resveratrol activates sirtuin 1, and thereafter, suppresses osteoclastogenic pathways, such as the receptor activator of the nuclear factor kappa B (RANK) ligand (RANKL) pathway, and promotes osteoblastogenic pathways, such as the wingless-related MMTV integration site pathway. Further, we noted that purified polyphenols and polyphenol-rich substances or extracts exert anti-inflammatory and/or antioxidative effects, which inhibit RANKL/RANK binding via the NF-κB pathway, resulting in the suppression of osteoclastogenesis. In conclusion, antioxidative and anti-inflammatory polyphenols, including resveratrol, can be safe and effective for the treatment of postmenopausal osteoporosis based on their ability to regulate the imbalance between bone formation and resorption.

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“…SIRT1 is highly expressed in ECs [ 19 ] and studies in mice show that aging lowers endothelial expression of SIRT1 while endothelial SIRT1 over-expression causes opposite effects, implying SIRT1 counteracts vascular aging [ 20 , 21 , 22 , 23 ]. Moreover, SIRT1 overexpression or pharmacological activation via SRT1720 has been shown to increase bone mass and decrease age-dependent bone loss [ 21 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. However, the role of SIRT1 as a potential therapeutic target to both counteract vascular aging in bone while improving bone healing remains to be investigated.…”

Section: Introductionmentioning

confidence: 99%

The Effects of SRT1720 Treatment on Endothelial Cells Derived from the Lung and Bone Marrow of Young and Aged, Male and Female Mice

Dadwal

¹

,

Bhatti

²

,

Awosanya

³

et al. 2021

IJMS

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Angiogenesis is critical for successful fracture healing. Age-related alterations in endothelial cells (ECs) may cause impaired bone healing. Therefore, examining therapeutic treatments to improve angiogenesis in aging may enhance bone healing. Sirtuin 1 (SIRT1) is highly expressed in ECs and its activation is known to counteract aging. Here, we examined the effects of SRT1720 treatment (SIRT1 activator) on the growth and function of bone marrow and lung ECs (BMECs and LECs, respectively), derived from young (3-4 month) and old (20–24 month) mice. While aging did not alter EC proliferation, treatment with SRT1720 significantly increased proliferation of all LECs. However, SRT1720 only increased proliferation of old female BMECs. Vessel-like tube assays showed similar vessel-like structures between young and old LECs and BMECs from both male and female mice. SRT1720 significantly improved vessel-like structures in all LECs. No age, sex, or treatment differences were found in migration related parameters of LECs. In males, old BMECs had greater migration rates than young BMECs, whereas in females, old BMECs had lower migration rates than young BMECs. Collectively, our data suggest that treatment with SRT1720 appears to enhance the angiogenic potential of LECs irrespective of age or sex. However, its role in BMECs is sex- and age-dependent.

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RETRACTED: Effect of resveratrol and mesenchymal stem cell monotherapy and combined treatment in management of osteoporosis in ovariectomized rats: Role of SIRT1/FOXO3a and Wnt/β-catenin pathways

Cited by 29 publications

References 74 publications

Evaluation of the Efficacy of Stem Cell Therapy in Ovariectomized Osteoporotic Rats Based on Micro-CT and Dual-Energy X-Ray Absorptiometry: A Systematic Review and Meta-Analysis

Evaluation of the Efficacy of Stem Cell Therapy in Ovariectomized Osteoporotic Rats Based on Micro-CT and Dual-Energy X-Ray Absorptiometry: A Systematic Review and Meta-Analysis

Anti-Osteoporotic Mechanisms of Polyphenols Elucidated Based on In Vivo Studies Using Ovariectomized Animals

The Effects of SRT1720 Treatment on Endothelial Cells Derived from the Lung and Bone Marrow of Young and Aged, Male and Female Mice

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