Bone responses in health and infectious diseases: A focus on osteoblasts

Terrier, Claire; Gasque, Philippe

doi:10.1016/j.jinf.2017.07.007

Cited by 44 publications

(34 citation statements)

References 91 publications

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“…However, in disease conditions, differentiation is inhibited in infected osteoblast and osteogenesis is disordered, contributing to bone destruction [41][42][43]. Upon exposure to bacterial or viral infection, osteoblasts can directly respond to pathogen-associated molecular patterns (PAMPs), such as LPS, with the release of several cytokines, including IL-1β, IL-6, and TNF-α [12,44]. Although it has been reported that alterations in METTL3 modulate the osteogenic lineage commitment and differentiation of BMSCs and are involved in osteoporosis [27], the role of m 6 A modification in osteoblast differentiation in an inflammatory environment remains unclear.…”

Section: Discussionmentioning

confidence: 99%

“…Osteoblasts possess the capacity to respond to an infectious challenge by activating the MAPK and NF-κB signaling pathways to regulate the expression of downstream proinflammatory cytokines, such as IL-6, IL-12, and TNF-α. The secretion of these proinflammatory factors contributes to controlling the inflammatory response and creates an osteolytic environment, which might influence the activities of other bone cells [12,51]. To explore the function of METTL3 in the osteoblast inflammatory response, we examined the accumulation of proinflammatory cytokines and LPS-induced signaling pathways molecules in METTL3-knockdown cells.…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that LPS can suppress osteoblastic differentiation by affecting multiple pathways, such as BMP/Smad signaling, Wnt/β-catenin signaling, and Notch signaling [8][9][10]. Moreover, LPS stimulates osteoblasts to produce various cytokines by activating mitogen-activated protein kinase (MAPK) signaling and nuclear factor-κB (NF-κB) signaling, thus contributing to the global systemic and local inflammatory responses [11,12].…”

Section: Introductionmentioning

confidence: 99%

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METTL3 Regulates Osteoblast Differentiation and Inflammatory Response via Smad Signaling and MAPK Signaling

Zhang

et al. 2019

IJMS

113

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Osteoblasts are crucial bone-building cells that maintain bone homeostasis, whereas inflammatory stimuli can inhibit osteogenesis and activate inflammatory response. N6-methyladenosine (m6A) is the most abundant mRNA modification in eukaryotes and plays important roles in multiple biological processes. However, whether m6A modification affects osteoblast differentiation and inflammatory response remains unknown. To address this issue, we investigated the expression of the N6-adenosine methyltransferase METTL3 and found that it was upregulated during osteoblast differentiation and downregulated after LPS stimulation. We then knocked down METTL3 and observed decreased levels of osteogenic markers, ALP activity, and mineralized nodules, as well as Smad1/5/9 phosphorylation, in LPS-induced inflammation. METTL3 knockdown promoted the mRNA expression and stability of negative regulators of Smad signaling, Smad7 and Smurf1, the same regulatory pattern identified when the m6A-binding protein YTHDF2 was silenced. Moreover, METTL3 depletion enhanced proinflammatory cytokine expression and increased the phosphorylation of ERK, p38, JNK, and p65 in MAPK and NF-κB signaling pathways. The increase in cytokine expression was inhibited after MAPK signaling inhibitor treatment. All data suggest that METTL3 knockdown inhibits osteoblast differentiation and Smad-dependent signaling by stabilizing Smad7 and Smurf1 mRNA transcripts via YTHDF2 involvement and activates the inflammatory response by regulating MAPK signaling in LPS-induced inflammation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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METTL3 Regulates Osteoblast Differentiation and Inflammatory Response via Smad Signaling and MAPK Signaling

Zhang

et al. 2019

IJMS

113

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“…Osteoblasts are crucial for the process of bone formation. Defects in osteoblast viability, differentiation and mineralization are among the major causes of osteoporosis (2,3). Puerarin, an isoflavone extracted from the Chinese medicine pueraria, exhibits protective functions on the cardiovascular system, nervous system, osteoporosis, liver injury, and inflammation in vivo and in vitro (4).…”

Section: Introductionmentioning

confidence: 99%

Puerarin promotes the viability and differentiation of MC3T3‑E1 cells by enhancing LC3B‑mediated autophagy through downregulation of miR‑204

et al. 2019

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Puerarin is a bioactive substance extracted from Pueraria lobata. It is known to promote the viability, differentiation and mineralization of osteoblasts. However, the molecular mechanisms involved in these activities are not well understood. The present study was conducted with the aim of elucidating the effect of puerarin on osteoblasts and to explore the underlying mechanism. CCK-8 analysis showed that puerarin (0.1, 1 and 10 µM) promoted the viability of osteoblastic MC3T3-E1 cells, with 1 µM of puerarin exhibiting the strongest effect. Moreover, 1 µM puerarin significantly increased the activity of alkaline phosphatase (ALP) and the formation of mineralized nodules in the MC3T3-E1 cells. Treatment with 1 µM puerarin for 72 h led to a significant upregulation in the expression level of microtubule-associated light chain 3 (LC3)B and Beclin1 proteins. This treatment was more effective in promoting LC3B expression than what was observed following treatment with rapamycin (overexpression for autophagy). The bilayer membrane structure of autophagosomes was observed by electron microscopy. Conversely, 3-methyladenine (3-MA, inhibitor of autophagy) reduced the cell viability as well as the activity of alkaline phosphatase (ALP) in MC3T3-E1 cells, although, there was no significant influence on mineralization. Prediction results of the biological information showed that LC3B could be a direct target of . In the present study, the expression level of miR-204 was decreased by puerarin. miR-204 mimics significantly decreased LC3B expression and inhibited auotophagosome formation, while the miR-204 inhibitor had the opposite effects. To conclude, the results of the present study suggest that puerarin promotes the viability and differentiation of MC3T3-E1 cells through autophagy, which is possibly associated with miR-204-regulated LC3B upregulation.

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“…4 Bone undergoes continuous remodeling throughout life, with osteoblasts responsible for bone formation while osteoclasts regulate bone resorption. 5,6 The osteoclast, as the main functional cell of bone resorption, plays a vital role in the loss of bone associated with the development of osteoporosis. 7 Osteolytic conditions occur, when the concerted processes of bone resorption and bone formation are dysfunctional, caused by enhanced osteoclast formation and function, or reduced osteoblast formation and function.…”

Section: Introductionmentioning

confidence: 99%

Achyranthes bidentata polysaccharide suppresses osteoclastogenesis and bone resorption via inhibiting RANKL signaling

Song

Cao

Huang

et al. 2018

J of Cellular Biochemistry

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Osteoclasts are highly differentiated multinucleated giant cells that play fundamental roles in bone resorption and in the pathogenesis of osteolytic conditions, such as osteoporosis and cancer-induced bone loss. Achyranthes bidentata polysaccharide (ABP) is a hydrophilic compound with anti-oxidation and anti-aging characteristics. The impact of ABP on RANKL-induced osteoclast formation and bone resorption has not been assessed, hence, in this study we investigated the effect of ABP on osteoclast formation and resorption in murine bone marrow derived osteoclasts. We found that ABP was able to suppress RANKL-induced osteoclast differentiation and bone resorption activity at concentrations above 6.5 µM, while demonstrating no cytotoxicity at concentrations up to 10 µM. The actions of ABP were mediated through inhibition of RANKL-induced c-Fos and NFATc1 gene and protein expression. Furthermore, we found that ABP suppressed NFATc1 transcriptional activity, and the phosphorylation of MAPK pathways induced by RANKL. Collectively, ABP attenuates RANKL-mediated osteoclast activity and signaling, and might serve as a potential therapeutic candidate for preventing bone loss related diseases.

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Bone responses in health and infectious diseases: A focus on osteoblasts

Cited by 44 publications

References 91 publications

METTL3 Regulates Osteoblast Differentiation and Inflammatory Response via Smad Signaling and MAPK Signaling

METTL3 Regulates Osteoblast Differentiation and Inflammatory Response via Smad Signaling and MAPK Signaling

Puerarin promotes the viability and differentiation of MC3T3‑E1 cells by enhancing LC3B‑mediated autophagy through downregulation of miR‑204

Achyranthes bidentata polysaccharide suppresses osteoclastogenesis and bone resorption via inhibiting RANKL signaling

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