Glucosamine Suppresses Osteoclast Differentiation through the Modulation of Glycosylation Including &lt;i&gt;O&lt;/i&gt;-GlcNAcylation

Takeuchi, Tomoharu; Sugimoto, Aya; Imazato, Nao; Tamura, Masahito; Nakatani, Sachie; Kobata, Kenji; Arata, Yoichiro

doi:10.1248/bpb.b16-00877

Cited by 19 publications

(20 citation statements)

References 24 publications

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“…Although the underlying molecular mechanism remains undetermined, it has been indicated in previous studies that PUGNAc treatment suppresses nuclear factor-kappaB (NF-κB) signaling pathway, which is important for osteoclast differentiation. 4,11) In addition, we identified vimentin as a potential O-GlcNAcylated protein in RAW264 cells (data not shown). Since O-GlcNAc modification of vimentin affects its function and antibody against citrullinated vimentin induces osteoclastogenesis, 18,19) it is possible that O-GlcNAcylation af- fects osteoclastogenesis through the modification of vimentin; this should be investigated in the future.…”

Section: Thiamet G Suppresses Osteoclast Differentiation and Bone Resmentioning

confidence: 92%

“…Differentiated cells were subjected to TRAP staining and TRAP-positive cells containing 3 or more nuclei were counted as described previously. 11) Human male PBMCs were seeded into a 96-well cell culture plate at a density of 1 × 10 5 cells/well. After 1 d, the cells were stimulated with 25 ng/mL human M-CSF (PeproTech, Rocky Hill, NJ, U.S.A.) and 50 ng/mL sRANKL in the presence of 10 µM Thiamet G. Then the cells were further cultured for 8 d to allow differentiation.…”

Section: Cell Culturementioning

confidence: 99%

“…[8][9][10] Moreover, it has been reported that GlcNAc, GlcN, and an O-GlcNAcase inhibitor PUGNAc, promote O-GlcNAcylation and suppress osteoclast differentiation. 11,12) However, GlcNAc and GlcN incorporation into cells affect sugar metabolism and PUGNAc inhibits not only O-GlcNAcase but also GH20 human β-hexosaminidases. 6,7) Therefore, it is uncertain whether the suppression of osteoclast differentiation by these chemicals occurs exclusively by the promotion of O-GlcNAcylation.…”

Section: Introductionmentioning

confidence: 99%

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Osteoclast Differentiation Is Suppressed by Increased <i>O</i>-GlcNAcylation Due to Thiamet G Treatment

Takeuchi

Horimoto

Oyama

et al. 2020

Biological & Pharmaceutical Bulletin

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Osteoclasts are the only bone-resorbing cells in organisms and understanding their differentiation mechanism is crucial for the treatment of osteoporosis. In the present study, we investigated the effect of Thiamet G, an O-GlcNAcase specific inhibitor, on osteoclastogenic differentiation. Thiamet G treatment increased global O-GlcNAcylation in murine RAW264 cells and suppressed receptor activator of nuclear factor-κB ligand (RANKL)-dependent formation in tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells, thereby suppressing the upregulation of osteoclast specific genes. Meanwhile, knockdown of O-linked N-acetylglucosamine (O-GlcNAc) transferase promoted the formation TRAP-positive multinuclear cells. Thiamet G treatment also suppressed RANKL and macrophage colony-stimulating factor (M-CSF) dependent osteoclast formation and bone-resorbing activity in mouse primary bone marrow cells and human peripheral blood mononuclear cells. These results indicate that the promotion of O-GlcNAc modification specifically suppresses osteoclast formation and its activity and suggest that chemicals affecting O-GlcNAc modification might potentially be useful in the prevention or treatment of osteoporosis in future.

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Section: Thiamet G Suppresses Osteoclast Differentiation and Bone Resmentioning

confidence: 92%

Section: Cell Culturementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Osteoclast Differentiation Is Suppressed by Increased <i>O</i>-GlcNAcylation Due to Thiamet G Treatment

Takeuchi

Horimoto

Oyama

et al. 2020

Biological & Pharmaceutical Bulletin

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“…Despite considerable knowledge of the biological activities of glucosamine (GlcN) including chondroprotective and anti-in ammatory action [1-7], its role in osteogenesis and bone tissue remains to be investigated in detail. The evidence collected so far on bone cells is mainly based on the use of monolayered non-human cell lines such as mouse MC3T3-E1 [14] and RAW 264.7 [21], fetal osteoblastic cell line hFOB1.19 [22], or animal models such as rat, mice or rabbit receiving GlcN oral administration [23][24][25].…”

Section: Discussionmentioning

confidence: 99%

Human Osteoclasts/Osteoblasts 3D Dynamic Co-Culture System to Study the Beneficial Effects of Glucosamine on Bone Microenvironment

Penolazzi

Lambertini

Pandolfi

et al. 2020

Preprint

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Background: Glucosamine (GlcN) functions as a building block of the cartilage matrix and its multifaceted roles in promoting joint health has been extensively investigated. On the contrary, the role of GlcN in osteogenesis and bone tissue is poorly understood, mainly due to the lack of adequate experimental models. Consequently, the benefit of GlcN in bone disorders remains controversial. In order to broaden the pharmacological relevance and potential therapeutic/nutraceutic efficacy of GlcN, we investigated the effect of GlcN on human primary osteoclasts (hOCs) and osteoblasts (hOBs) that were grown with 2D traditional methods or co-cultured in a more complex culture system one step closer to the in vivo bone microenvironment, consisting in a three-dimensional (3D) dynamic system.Methods: Osteoclasts derived from peripheral blood monocytes (hMCs) of either healthy or osteoarthritis (OA) donors, were used and kept in culture with osteoclastogenic inducers. hMCs were also combined with hOBs in a 3D dynamic co‐culture system by using RCCS-4TM bioreactor in osteogenic medium without osteoclastogenic inducers. In this condition osteoclastogenesis was supported by hOBs and sizeable self assembling aggregates were obtained. The differentiated osteoclasts were evaluated by the tartrate-resistant acid phosphatase assay, osteogenic differentiation was monitored by analyzing mineral matrix deposition through Alizarin Red staining, and expression of osteogenic markers through RT-qPCR. The cells were treated with DONA® Crystalline Glucosamine Sulfate (i.e. the original GlcN sulfate product).Results: DONA® was effective in decreasing the hOCs differentiation and function. Osteoclasts from OA donors were more sensitive than those from healthy donors. At the same time, DONA® showed anabolic effects on osteoblasts both in 2D conventional cell culture and in osteoclasts/osteoblasts 3D dynamic co-culture system.Conclusions: Here we demonstrated the effectiveness of a 3D dynamic co-culture system to provide useful information on the spectrum of action of GlcN on bone microenvironment. This can pave the way to better define the potential applications of a compound such as GlcN which is positioned between pharmaceuticals and nutraceuticals. Therefore, based on our observations, we hypothesize that GlcN could have potential benefits either in the treatment of osteopenic diseases such as osteoporosis, or in the bone health maintenance.

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“…It is believed that GS has a role in rebuilding the damaged cartilage by stimulating the production of proteoglycans by fibroblasts and chondrocytes [8]. Likewise, a plethora of experimental studies have demonstrated that GS can modulate the cytokine-mediated pathways regulating inflammation [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

The impact of pharmaceutical care on the efficacy and safety of transdermal glucosamine sulfate and capsaicin for joint pain

et al. 2020

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Background Arthritis is a common chronic joint disease. It progressively causes joint pain, stiffness, and disability. Glucosamine sulfate has been shown to be an effective symptom-relieving biological agent. Pharmaceutical care, including patient counseling, is very important to overcome inconsistencies in compliance and adherence. Objective The aim of this study is to evaluate the impact of pharmaceutical care on the efficacy and safety of transdermal glucosamine sulfate and capsaicin (TGC-Plus cream) in the management of chronic joint pain. Settings A rheumatology outpatient clinic, Jordan University Hospital, Amman, Jordan. Methods A cross sectional study with a single treatment group was conducted. One hundred (100) patients diagnosed with either osteoarthritis, rheumatoid arthritis or chronic joint pains were recruited. Patients started on TGC-Plus cream applied twice daily for duration of 12 weeks. Patients received pharmaceutical care services during the study duration. Main outcome measure Efficacy and safety of TGC-Plus cream in pain relief and joint function improvement (alleviating joint stiffness) the need of alternative analgesics and number of doctor's visits. Results There was a significant reduction of numerical pain score (7 ± 1.40 vs. 3.53 ± 2.13, p < 0.05), with significant reduction in the limitation of joint movement (6.18 ± 2.14 vs. 3.47 ± 2.23, p < 0.05) after 12 weeks. In addition, the need for analgesics and the number of doctor's visits were significantly reduced (1.99 ± 2.77 vs. 0.71 ± 1.90, p < 0.05), (1.11 ± 1.28 vs. 0.06 ± 0.293, p < 0.05) respectively. Conclusion Pharmacist supervised treatment with the TGC-Plus cream significantly reduces pain and enhances locomotor function in patients with chronic pain who failed to achieve adequate prior pain relief.

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Glucosamine Suppresses Osteoclast Differentiation through the Modulation of Glycosylation Including <i>O</i>-GlcNAcylation

Cited by 19 publications

References 24 publications

Osteoclast Differentiation Is Suppressed by Increased <i>O</i>-GlcNAcylation Due to Thiamet G Treatment

Osteoclast Differentiation Is Suppressed by Increased <i>O</i>-GlcNAcylation Due to Thiamet G Treatment

Human Osteoclasts/Osteoblasts 3D Dynamic Co-Culture System to Study the Beneficial Effects of Glucosamine on Bone Microenvironment

The impact of pharmaceutical care on the efficacy and safety of transdermal glucosamine sulfate and capsaicin for joint pain

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