GPR39 agonist TC-G 1008 promotes osteoblast differentiation and mineralization in MC3T3-E1 cells

Chai, Xingyu; Zhang, Wencan; Chang, Bingying; Feng, Xianli; Song, Jing; Li, Le; Yu, Chengbin; Zhao, Junyong; Si, Huaijun

doi:10.1080/21691401.2019.1649270

Cited by 25 publications

(18 citation statements)

References 25 publications

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“…However, discussed results were inconsistent and contradictory, indicating that miR-21 may promote, as well as inhibit osteogenic differentiation, what can be correlated with diverse cellular plasticity of MSCs and their origin. To minimize this issue, we used the model of pre-osteoblast MC3T3 cell line that represents a stable and reproducible model for studies related with signaling pathways crucial for proliferation and differentiation of osteoblast [37][38][39][40][41]. Furthermore, under osteogenic conditions MC3T3 pre-osteoblasts synthesize and assemble collagenous extracellular matrix with organization and mineralization that resembles bone [37].…”

Section: Discussionmentioning

confidence: 99%

The Role of miR-21 in Osteoblasts–Osteoclasts Coupling In Vitro

Śmieszek

Marcinkowska

Pielok

et al. 2020

Cells

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MiR-21 is being gradually more and more recognized as a molecule regulating bone tissue homeostasis. However, its function is not fully understood due to the dual role of miR-21 on bone-forming and bone-resorbing cells. In this study, we investigated the impact of miR-21 inhibition on pre-osteoblastic cells differentiation and paracrine signaling towards pre-osteoclasts using indirect co-culture model of mouse pre-osteoblast (MC3T3) and pre-osteoclast (4B12) cell lines. The inhibition of miR-21 in MC3T3 cells (MC3T3inh21) modulated expression of genes encoding osteogenic markers including collagen type I (Coll-1), osteocalcin (Ocl), osteopontin (Opn), and runt-related transcription factor 2 (Runx-2). Inhibition of miR-21 in osteogenic cultures of MC3T3 also inflected the synthesis of OPN protein which is essential for proper mineralization of extracellular matrix (ECM) and anchoring osteoclasts to the bones. Furthermore, it was shown that in osteoblasts miR-21 regulates expression of factors that are vital for survival of pre-osteoclast, such as receptor activator of nuclear factor κB ligand (RANKL). The pre-osteoclast cultured with MC3T3inh21 cells was characterized by lowered expression of several markers associated with osteoclasts’ differentiation, foremost tartrate-resistant acid phosphatase (Trap) but also receptor activator of nuclear factor-κB ligand (Rank), cathepsin K (Ctsk), carbonic anhydrase II (CaII), and matrix metalloproteinase (Mmp-9). Collectively, our data indicate that the inhibition of miR-21 in MC3T3 cells impairs the differentiation and ECM mineralization as well as influences paracrine signaling leading to decreased viability of pre-osteoclasts.

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Section: Discussionmentioning

confidence: 99%

The Role of miR-21 in Osteoblasts–Osteoclasts Coupling In Vitro

Śmieszek

Marcinkowska

Pielok

et al. 2020

Cells

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“…Along the cascade of AMPK activation, MF can influence its osteogenesis activity through Runx2 [37]. This will cause mature osteocyte formation and proper bone mineralization [38] Some studies prove these osteogenic effects. MF is shown to decrease bone turnover when compared with other anti-diabetic medications [48].…”

Section: Effect Of Metformin On Osteogenesis (Ampk-dependent Pathway)mentioning

confidence: 99%

“…AMPK induces these effects through the runt-related transcription factor Runx2 [37], which is vital for the maturation of chondrocyte and healthy skeletal formation [22]. Also, the inhibition of AMPK led to a decrease in the production of alkaline phosphatase, osteocalcin, and type-1 collagen, all of which are important for good quality bone formation [38]. It is also shown that AMPK inhibition would lead to decreased cellular activity of alkaline phosphatase and Runx2 [38].…”

Section: Ampk and Osteogenesismentioning

confidence: 99%

“…Also, the inhibition of AMPK led to a decrease in the production of alkaline phosphatase, osteocalcin, and type-1 collagen, all of which are important for good quality bone formation [38]. It is also shown that AMPK inhibition would lead to decreased cellular activity of alkaline phosphatase and Runx2 [38].…”

Section: Ampk and Osteogenesismentioning

confidence: 99%

“…As a regulator of metabolic activity, many researchers started to appreciate the role of AMPK and tried to target this pathway as a treatment of many metabolic diseases such as DM and OS. Many substances have been shown to have activity on AMPK [16,20,38,42]. Among them, MF, which is already being used as a first-line medication for DM, shows a positive regulation effect of AMPK [37,[42][43].…”

Section: Ampk=amp Activated Protein Kinase; Amp=adenosine Monophosphatementioning

confidence: 99%

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The Future of Metformin in the Prevention of Diabetes-Related Osteoporosis

Aung¹,

Amin²,

Gulraiz³

et al. 2020

Cureus

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As a worldwide aging population is on the rise, osteoporosis (OS) is becoming a global health burden. Therefore, many researchers and health authorities are looking into the potential prevention and treatment of OS. Although previously regarded as two separate pathological processes, diabetes (DM) and OS are now regarded as two conditions that can occur together. It is now believed that OS can develop as a complication of DM. This relationship is further evidenced through a reduction in bone mineral density in type-1 diabetes with a resulting increased risk of fracture. Although bone mineral density in type-2 diabetes mellitus is normal or increased, there is also increased fragility due to decreased bone quality. These abnormal bone qualities tend to occur through the production of reduced bone microvasculature and advanced glycation end product, AGE. Interestingly, one of the most common treatments for DM, metformin (MF), shows a promising result on the protection of diabetes and non-diabetes related bone turnover. It is believed that MF modulates its effect through the adenosine monophosphate-activated protein kinase (AMPK) pathway. Recent data regarded AMPK as a vital mediator of homeostasis. It is involved not only in glucose metabolism but also in osteogenesis. AMPK can directly influence the production of mature and good quality bone by decreasing osteoclasts, increasing osteoblast formation, and enhancing bone mineral deposition. As an activator of AMPK, MF also upregulates osteogenesis. Furthermore, MF can influence osteogenesis through a non-AMPK pathway, such as the fructose 1-6 phosphatase pathway, by reducing glucose levels. While already recognized as a safe and effective treatment for DM, this article discusses whether MF can be used for the prevention and treatment of OS.

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GPR39 promotes cardiac hypertrophy by regulating the AMPK–mTOR pathway and protein synthesis

Liao

Gao

et al. 2021

Cell Biology International

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Hypertrophic growth of the cardiomyocytes is one of the core mechanisms underlying cardiac hypertrophy. However, the mechanism underlying cardiac hypertrophy remains not fully understood. Here we provided evidence that G protein‐coupled receptor 39 (GPR39) promotes cardiac hypertrophy via inhibiting AMP‐activated protein kinase (AMPK) signaling. GRP39 expression is overexpressed in hypertrophic hearts of humans and transverse aortic constriction (TAC)‐induced cardiac hypertrophy in mice. In neonatal cardiomyocytes, adenovirus‐mediated overexpression of GPR39 promoted angiotensin II‐induced cardiac hypertrophy, while GPR39 knockdown repressed hypertrophic response. Adeno‐associated virus 9‐mediated knockdown of GPR39 suppressed TAC‐induced decline in fraction shortening and ejection fraction, increase in heart weight and cardiomyocyte size, as well as overexpression of hypertrophic fetal genes. A mechanism study demonstrated that GPR39 repressed the activation of AMPK to activate the mammalian target of rapamycin (mTOR) and ribosomal protein S6 kinase β‐1 (S6K1), subsequently promoted de novo protein synthesis. Inhibition of mTOR with rapamycin blocked the effects of GPR39 overexpression on protein synthesis and repressed cardiac hypertrophy. Collectively, our findings demonstrated that GPR39 promoted cardiac hypertrophy via regulating the AMPK–mTOR–S6K1 signaling pathway, and GRP39 can be targeted for the treatment of cardiac hypertrophy.

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GPR39 agonist TC-G 1008 promotes osteoblast differentiation and mineralization in MC3T3-E1 cells

Cited by 25 publications

References 25 publications

The Role of miR-21 in Osteoblasts–Osteoclasts Coupling In Vitro

The Role of miR-21 in Osteoblasts–Osteoclasts Coupling In Vitro

The Future of Metformin in the Prevention of Diabetes-Related Osteoporosis

GPR39 promotes cardiac hypertrophy by regulating the AMPK–mTOR pathway and protein synthesis

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