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UNIVERSITY OF SOUTHERN DENMARK

O- GlcNAcylation promotes osteoclastogenesis and dictates the resorption mode by osteoclasts

Ph.D : Thaise Mayumi Taira Supervisor: Prof. Dr. Sandra Yasuyo Fukada

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UNIVERSITY OF SÃO PAULO SCHOOL OF PHARMACEUTICAL SCIENCES OF RIBEIRÃO PRETO

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Trap MMP-9 CtsK Boyle et al., 2003 Kalervo-Vaananen et al., 2008 Qin et al., 2012 Teti, 2013

Glucose HEXOSAMINE BIOSYNTHETIC PATHWAY (HBP)

ATP

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ATP

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What is the role of O- GlcNAcylation on osteoclastogenesis ?

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Evaluate the role of O-GlcNAcylation on osteoclast’s differentiation and function.

AIM

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L:\PATO\Klinisk Cellebiologi\Thaise\Results\OCVideo 02-TMT-19 OSMI-1 and O-GlcNAc differentiation resorption\OCfusion-02-TMT-19-OSMI-1, O-GlcNAc TRACP activity\OCfusion 02-TMT-19 O-GlcNAc pictures\10B_Control 10x.tif

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GlcNAc (0.3 mM )

O- GlcNAcylation participates on osteoclasts differentiation and fusion

* Paper under review

A

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L:\PATO\Klinisk Cellebiologi\Thaise\Results\OCVideo 02-TMT-19 OSMI-1 and O-GlcNAc differentiation resorption\OCfusion-02-TMT-19-OSMI-1, O-GlcNAc TRACP activity\OCfusion 02-TMT-19 O-GlcNAc pictures\10B_Control 10x.tif

L:\PATO\Klinisk Cellebiologi\Thaise\Results\OCVideo 02-TMT-19 OSMI-1 and O-GlcNAc differentiation resorption\OCfusion-02-TMT-19-OSMI-1, O-GlcNAc TRACP activity\OCfusion 02-TMT-19 O-GlcNAc pictures\6C_0.03mM O-GlcNAc 10x.tif

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GlcNAc (0.3 mM )

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L:\PATO\Klinisk Cellebiologi\Thaise\Results\OCVideo 02-TMT-19 OSMI-1 and O-GlcNAc differentiation resorption\OCfusion-02-TMT-19-OSMI-1, O-GlcNAc TRACP activity\Ofusion 02-TMT-19 OSMI-1 pictures\3E Control 10x.tif

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OSMI-1 (30 nM )

O- GlcNAcylation participates on osteoclasts differentiation and fusion

* Paper under review

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B

(OGT inhibitor )

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L:\PATO\Klinisk Cellebiologi\Thaise\Results\OCVideo 02-TMT-19 OSMI-1 and O-GlcNAc differentiation resorption\OCreesorption 02-TMT-19 pictures of bone slices\OCresorption 02-TMT-19 O-GlcNAc\A4 0.03mM O-GlcNAc 20x.tif

L:\PATO\Klinisk Cellebiologi\Thaise\Results\OCVideo 02-TMT-19 OSMI-1 and O-GlcNAc differentiation resorption\OCreesorption 02-TMT-19 pictures of bone slices\OCresorption 02-TMT-19 O-GlcNAc\B8 Control 20x.tif

O- GlcNAcylation affects the type of osteoclasts resorption

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GlcNAc (0.3 mM )

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* Paper under review

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L:\PATO\Klinisk Cellebiologi\Thaise\Results\OCVideo 02-TMT-19 OSMI-1 and O-GlcNAc differentiation resorption\OCreesorption 02-TMT-19 pictures of bone slices\OCresorption 02-TMT-19 O-GlcNAc\A4 0.03mM O-GlcNAc 20x.tif

L:\PATO\Klinisk Cellebiologi\Thaise\Results\OCVideo 02-TMT-19 OSMI-1 and O-GlcNAc differentiation resorption\OCreesorption 02-TMT-19 pictures of bone slices\OCresorption 02-TMT-19 O-GlcNAc\B8 Control 20x.tif

O- GlcNAcylation affects the type of osteoclasts resorption

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GlcNAc (0.3 mM )

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OSMI-1 (30 nM )

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B

* Paper under review

(OGT inhibitor )

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Control

GlcNAc 0.03 mM

Bone and Osteoclasts

O- GlcNAcylation affects the type of osteoclasts resorption

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Control

GlcNAc 0.03 mM

Bone and Osteoclasts

O- GlcNAcylation affects the type of osteoclasts resorption

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Control

OSMI-1 1 n M

O- GlcNAcylation affects the type of osteoclasts resorption

Bone and Osteoclasts

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Control

OSMI-1 1 n M

O- GlcNAcylation affects the type of osteoclasts resorption

Bone and Osteoclasts

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✓ O- GlcNAcylation stimulates osteoclastogenesis in vitro; ✓ O- GlcNAcylation coordinates osteoclasts’s agressiveness for bone resorption .

CONCLUSION

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Acknowledgment

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Profa. Sandra Y . Fukada – Supervisor (FCFRP-USP) Prof. Kent Søe - Colaborador (SDU – Denmark ) Prof. Erivan Shineider Ramos Junior – Colaborator (Augusta University ) Cecília Costa do Carmo e Silva – Student (FCFRP-USP) Mayara Santos Gomes – Laboratory Technitian (FCFRP-USP) Jacob Bastholm Olesen – Laboratory Technitian (SDU)

Thank you for your attention !

t haise.taira@usp.br

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oop | Erivan Schnaider Ramos-Junior