Andrographolide modulates OPG/RANKL axis to promote osteoblastic differentiation in MC3T3-E1 cells and protects bone loss during estrogen deficiency in rats

Tantikanlayaporn, Duangrat; Wichit, Patsorn; Suksen, Kanoknetr; Suksamrarn, Apichart; Piyachaturawat, Pawinee

doi:10.1016/j.biopha.2020.110763

Cited by 18 publications

(10 citation statements)

References 44 publications

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“…It also stimulated the differentiation and survival of OBs, which increased bone deposition. Meanwhile, the study confirmed that andrographolide prevented bone loss and improved bone turnover rate in OVX rat model ( 49 ).…”

Section: Natural Terpenoids Against Opmentioning

confidence: 62%

Evolving Roles of Natural Terpenoids From Traditional Chinese Medicine in the Treatment of Osteoporosis

Zhuo

Jiang

et al. 2022

Front. Endocrinol.

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Osteoporosis (OP) is a systemic metabolic skeletal disease which can lead to reduction in bone mass and increased risk of bone fracture due to the microstructural degradation. Traditional Chinese medicine (TCM) has been applied in the prevention and treatment of osteoporosis for a long time. Terpenoids, a class of natural products that are rich in TCM, have been widely studied for their therapeutic efficacy on bone resorption, osteogenesis, and concomitant inflammation. Terpenoids can be classified in four categories by structures, monoterpenoids, sesquiterpenoids, diterpenoids, and triterpenoids. In this review, we comprehensively summarize all the currently known TCM-derived terpenoids in the treatment of OP. In addition, we discuss the possible mechanistic-of-actions of all four category terpenoids in anti-OP and assess their therapeutic potential for OP treatment.

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Section: Natural Terpenoids Against Opmentioning

confidence: 62%

Evolving Roles of Natural Terpenoids From Traditional Chinese Medicine in the Treatment of Osteoporosis

Zhuo

Jiang

et al. 2022

Front. Endocrinol.

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“…Ca 2+ release from the ER through the IP3R channel and Ca 2+ influx via the SOCE pathway contributed to the development of ER stress in osteoblasts (Zhang et al 2020 ). Additionally, LPZ treatment was associated with a reduction in the ratio of OPG/Rankl, which has been previously shown to be an indication of bone formation or bone resorption (Tantikanlayaporn et al 2020 ). We hypothesized that LPZ may destroy the dynamic balance between OB bone formation and OC bone resorption, stimulating bone resorption rather than bone formation.…”

Section: Discussionmentioning

confidence: 72%

Lansoprazole-induced osteoporosis via the IP3R- and SOCE-mediated calcium signaling pathways

Cheng

Sun

et al. 2022

Mol Med

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Background Many clinical studies have shown a correlation between proton pump inhibitors (PPIs) and osteoporosis or fractures. The purpose of this study was to establish a murine model of chronic oral PPI administration to verify whether PPIs caused bone metabolic impairment and investigate the relevant molecular mechanism underlying the effects of PPIs on MC3T3-E1 murine osteoblasts. Methods A lansoprazole-induced bone loss model was used to investigate the damaging effects of PPIs. In vivo, immunohistochemistry, Hematoxylin–Eosin (HE) staining, micro-CT analysis, and blood biochemical analyses were used to evaluate the effect of lansoprazole on bone injury in mice. In vitro, the effects of lansoprazole and related signaling pathways in MC3T3-E1 cells were investigated by CCK-8 assays, EdU assays, flow cytometry, laser confocal microscopy, patch clamping, reverse transcription-quantitative polymerase chain reaction and Western blotting. Results After 6 months of lansoprazole gavage in ICR mice, the micro-CT results showed that compared with that in the vehicle group, the bone mineral density (BMD) in the high-dose group was significantly decreased (P < 0.05), and the bone microarchitecture gradually degraded. Biochemical analysis of bone serum showed that blood calcium and phosphorus were both decreased (P < 0.01). We found that long-term administration of lansoprazole impaired skeletal function in mice. In vitro, we found that lansoprazole (LPZ) could cause calcium overload in MC3T3-E1 cells leading to apoptosis, and 2-APB, an inhibitor of IP3R calcium release channel and SOCE pathway, effectively blocked increase in calcium caused by LPZ, thus protecting cell viability. Conclusions Longterm administration of LPZ induced osteoporotic symptoms in mice, and LPZ triggered calcium increases in osteoblasts in a concentration-dependent manner. Intracellular calcium ([Ca2+]i) persisted at a high concentration, thereby causing endoplasmic reticulum stress (ERS) and inducing osteoblast apoptosis.

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“…Previously, AP has been shown to have pro-osteogenic effects on bone marrow stem cells of mice and rats, whereas it prevented TNFα-induced suppression of osteoblast formation and mineralization [33]. Also, we recently reported that AP enhanced the osteogenic capacity of mouse pre-osteoblast cell lines [31]. However, the effect of AP on the proliferation and osteogenic differentiation of PL-hMSCs are still unknown.…”

Section: Discussionmentioning

confidence: 99%

“…AP has been examined in various experimental studies on humans and animals indicating that it is safe and has less serious side effects [25,30]. Recently, we have reported the osteogenic effect of AP in mouse preosteoblast cell lines and the protective effect on bone loss in estrogen-de cient rats [31]. However, the effects of AP on PL-hMSCs are still unknown.…”

Section: Pl-hmscs Have Been Reported To Have the Characteristics Matcmentioning

confidence: 99%

Andrographolide Promotes Proliferative and Osteogenic Potentials of Human Placenta-Derived Mesenchymal Stem Cells Through the Activation of Wnt/β-Catenin Signaling.

Phunikom

Boonmeun

Suksen

et al. 2021

Preprint

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IntroductionThe in vitro expansion and differentiation of mesenchymal stem cells derived from bone marrow (BM-hMSCs) are considered as potential therapeutic tools for clinical applications in bone tissue engineering and regenerative medicine. However, invasive sampling and reduction in number and proliferative capacity with age are the major limitations of BM-hMSCs. Recently, human placenta-derived MSCs (PL-hMSCs) obtained by a non-invasive procedure have attracted much interest. Attempts to increase the potential of PL-hMSCs would be an important paradigm in regenerative medicine. Herein, we examined the proliferative and osteogenic effect of andrographolide (AP) on PL-hMSCs. MethodsMesenchymal stem cells were isolated from full-term normal human placentas and were characterized before using. Cell cytotoxicity and proliferative effect of AP were examined by MTT and BrdU assay, respectively. The non-toxicity concentrations of AP were further assessed for osteogenic effect determined by alkaline phosphatase (ALP) expression and activity, alizarin red staining, and osteoblast-specific gene expressions. Screening of genes involved in osteogenic differentiation related pathways modulated by AP were explored by a NanoString nCounter analysis. ResultsPL-hMSCs generated in this study met the MSCs criteria set by the International Society of Cellular Therapy. AP has no cytotoxic effect on PL-hMSCs up to 10 μM. The compound increased PL-hMSCs proliferation concomitant with increases in Wnt/ β-catenin level and activity. It also enhanced osteogenic differentiation in association with osteoblast-specific mRNA expression. Further, AP promoted bone formation and increased bone structural protein level, osteocalcin, in osteoblastic cells. Gene screening analysis showed the upregulation of genes related to Wnt/β-catenin, TGFβ/BMP, SMAD and FGF signaling pathways. ConclusionWe demonstrated, for the first time, the potential role of AP in promoting proliferation, osteogenic differentiation, and osteoblast bone formation of PL-hMSCs. This study suggests that AP may be an effective novel agent for the improvement of PL-hMSCs and stem cell-based therapy for bone regeneration.

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Andrographolide modulates OPG/RANKL axis to promote osteoblastic differentiation in MC3T3-E1 cells and protects bone loss during estrogen deficiency in rats

Cited by 18 publications

References 44 publications

Evolving Roles of Natural Terpenoids From Traditional Chinese Medicine in the Treatment of Osteoporosis

Evolving Roles of Natural Terpenoids From Traditional Chinese Medicine in the Treatment of Osteoporosis

Lansoprazole-induced osteoporosis via the IP3R- and SOCE-mediated calcium signaling pathways

Andrographolide Promotes Proliferative and Osteogenic Potentials of Human Placenta-Derived Mesenchymal Stem Cells Through the Activation of Wnt/β-Catenin Signaling.

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