Zoledronate and lipopolysaccharide suppress osteoblast differentiation through downregulating phosphorylation of Smad in pre-osteoblastic MC3T3-E1 cells

Amamoto, Shinsuke; Yoshiga, Daigo; Tabe, Shirou; Kokabu, Shoichiro; Fujii, Wataru; Hikiji, Hisako; Tominaga, Kazuhiro; Yoshioka, Izumi

doi:10.1016/j.ajoms.2022.01.007

Cited by 2 publications

(3 citation statements)

References 55 publications

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“…In contrast, Xu and colleagues reported that low concentrations of LPS induced osteoblast proliferation and accelerated fracture healing through the NF-κB signaling pathway in vitro [39]. The inhibitory effect of LPS on osteoblast differentiation by targeting the BMP2/Smad signaling pathway has been reported [40]. Osteoblast-associated genes including Alpl, Ibsp, Col1a1, and Runx2 were downregulated by LPS, leading to a decrease in ALP activity and in vitro mineralization [40].…”

Section: Discussionmentioning

confidence: 99%

“…The inhibitory effect of LPS on osteoblast differentiation by targeting the BMP2/Smad signaling pathway has been reported [40]. Osteoblast-associated genes including Alpl, Ibsp, Col1a1, and Runx2 were downregulated by LPS, leading to a decrease in ALP activity and in vitro mineralization [40]. Creb5 stimulated osteoblast differentiation and the anabolic action of PTH was mediated by Creb transactivation of BMP 2 expression in bones [41].…”

Section: Discussionmentioning

confidence: 99%

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Lipopolysaccharide Impedes Bone Repair in FcγRIIB-Deficient Mice

Jantaboon,

Sakunrangsit,

Toejing

et al. 2023

IJMS

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Chronic inflammation contributes to the development of skeletal disorders in patients with systemic lupus erythematosus (SLE). Activation of the host immune response stimulates osteoclast activity, which in turn leads to bone loss. Regenerating bone in the inflammatory microenvironments of SLE patients with critical bone defects remains a great challenge. In this study, we utilized lipopolysaccharide (LPS) to imitate locally and systemically pathogenic bacterial infection and examined the bone regeneration performance of LPS-associated mandibular and tibial bone regeneration impairment in FcγRIIB−/− mice. Our results indicated that a loss of FcγRIIB alleviates bone regeneration in both mandibles and tibiae. After LPS induction, FcγRIIB−/− mice were susceptible to impaired fracture healing in tibial and mandibular bones. LPS decreased the mineralization to collagen ratio in FcγRIIB−/− mice, indicating a mineralization defect during bone repair. An osteoblast-associated gene (Col1a1) was attenuated in FcγRIIB-deficient mice, whereas Bglap, Hhip, and Creb5 were further downregulated with LPS treatment in FcγRIIB−/− mice compared to FcγRIIB−/− mice. Alpl and Bglap expression was dcreased in osteoblasts derived from bone chips. An osteoclast-associated gene, Tnfsf11/Tnfrsf11 ratio, ewas increased in LPS-induced FcγRIIB−/− mice and in vitro. Furthermore, systemic LPS was relatively potent in stimulating production of pro-inflammatory cytokines including TNF-α, IL-6, and MCP-1 in FcγRIIB−/− mice compared to FcγRIIB−/− mice. The levels of TNF-α, IFN-β, IL-1α, and IL-17A were increased, whereas IL-10 and IL-23 were decreased in FcγRIIB−/− mice treated locally with LPS. These findings suggest that both local and systemic LPS burden can exacerbate bone regeneration impairment, delay mineralization and skeletal repair, and induce inflammation in SLE patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide Impedes Bone Repair in FcγRIIB-Deficient Mice

Jantaboon,

Sakunrangsit,

Toejing

et al. 2023

IJMS

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“…Lipopolysaccharide (LPS), a component of the cell wall in Gram-negative bacteria, is widely used to mimic Gram-negative bacterial infections in cell and animal models. Many studies have demonstrated that LPS can inhibit osteoblast differentiation in MC3T3-E1 cells [23] by intracellular signaling, including Wnt/β-catenin, p38, Smad, and other signal transduction pathways [24][25][26][27].…”

Section: Effect Of Nicotinamide Mononucleotide On Osteogenesis In Mc3...mentioning

confidence: 99%

Effect of nicotinamide mononucleotide on osteogenesis in MC3T3-E1 cells against inflammation-induced by lipopolysaccharide

Kang,

Koo,

Jun

et al. 2024

Clin Exp Reprod Med

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Objective: Nicotinamide mononucleotide (NMN) is extensively utilized as an anti-aging agent and possesses anti-inflammatory properties. Lipopolysaccharide (LPS) activates Toll-like receptor 4, a process modulated by intracellular signaling pathways such as the Wnt/β-catenin pathway. This study investigated the impact of NMN on osteogenesis in the presence of LPS. Methods: To elucidate the role of NMN in osteogenesis in the context of Gram-negative bacterial infection after LPS treatment, we cultured a mouse pre-osteoblast cell line (MC3T3-E1) and subsequently incubated it with NMN and/or LPS. We then evaluated osteogenic activity by measuring alkaline phosphatase activity, assessing gene expression and protein levels, and performing Alizarin Red S staining and immunocytochemistry.Results: MC3T3-E1 cells underwent successful differentiation into osteoblasts following treatment with osteogenic induction medium. LPS diminished features related to osteogenic differentiation, which were subsequently partially reversed by treatment with NMN. The restorative effects of NMN on LPS-exposed MC3T3-E1 cells were further substantiated by elucidating the role of Wnt/β-catenin signaling, as confirmed through immunocytochemistry. Conclusion: This study showed that infection with Gram-negative bacteria disrupted the osteogenic differentiation of MC3T3-E1 cells. This adverse effect was partially reversed by administering a high-dose of NMN. Drawing on these results, we propose that NMN could serve as a viable therapeutic strategy to preserve bone homeostasis in elderly and immunocompromised patients.

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Zoledronate and lipopolysaccharide suppress osteoblast differentiation through downregulating phosphorylation of Smad in pre-osteoblastic MC3T3-E1 cells

Cited by 2 publications

References 55 publications

Lipopolysaccharide Impedes Bone Repair in FcγRIIB-Deficient Mice

Lipopolysaccharide Impedes Bone Repair in FcγRIIB-Deficient Mice

Effect of nicotinamide mononucleotide on osteogenesis in MC3T3-E1 cells against inflammation-induced by lipopolysaccharide

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