Anti-RANKL treatment inhibits erosive joint destruction and lowers inflammation but has no effect on bone formation in the delayed-type hypersensitivity arthritis (DTHA) model

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Anti-RANKL treatment inhibits erosive joint destruction and lowers inflammation but has no effect on bone formation in the delayed-type hypersensitivity arthritis (DTHA) model. / Atkinson, Sara Marie; Bleil, Janine; Maier, Rene; Kuehl, Anja A.; Thorn, Mette; Serikawa, Kyle; Fox, Brian; Kruse, Kim; Haase, Claus; Skov, Soren; Nansen, Anneline; Syrbe, Uta.

In: Arthritis Research & Therapy, Vol. 18, 28, 23.01.2016.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Atkinson, SM, Bleil, J, Maier, R, Kuehl, AA, Thorn, M, Serikawa, K, Fox, B, Kruse, K, Haase, C, Skov, S, Nansen, A & Syrbe, U 2016, 'Anti-RANKL treatment inhibits erosive joint destruction and lowers inflammation but has no effect on bone formation in the delayed-type hypersensitivity arthritis (DTHA) model', Arthritis Research & Therapy, vol. 18, 28. https://doi.org/10.1186/s13075-016-0931-3

APA

Atkinson, S. M., Bleil, J., Maier, R., Kuehl, A. A., Thorn, M., Serikawa, K., Fox, B., Kruse, K., Haase, C., Skov, S., Nansen, A., & Syrbe, U. (2016). Anti-RANKL treatment inhibits erosive joint destruction and lowers inflammation but has no effect on bone formation in the delayed-type hypersensitivity arthritis (DTHA) model. Arthritis Research & Therapy, 18, [28]. https://doi.org/10.1186/s13075-016-0931-3

Vancouver

Atkinson SM, Bleil J, Maier R, Kuehl AA, Thorn M, Serikawa K et al. Anti-RANKL treatment inhibits erosive joint destruction and lowers inflammation but has no effect on bone formation in the delayed-type hypersensitivity arthritis (DTHA) model. Arthritis Research & Therapy. 2016 Jan 23;18. 28. https://doi.org/10.1186/s13075-016-0931-3

Author

Atkinson, Sara Marie ; Bleil, Janine ; Maier, Rene ; Kuehl, Anja A. ; Thorn, Mette ; Serikawa, Kyle ; Fox, Brian ; Kruse, Kim ; Haase, Claus ; Skov, Soren ; Nansen, Anneline ; Syrbe, Uta. / Anti-RANKL treatment inhibits erosive joint destruction and lowers inflammation but has no effect on bone formation in the delayed-type hypersensitivity arthritis (DTHA) model. In: Arthritis Research & Therapy. 2016 ; Vol. 18.

Bibtex

@article{792ff35700434293a27aaef7ea22e10a,
title = "Anti-RANKL treatment inhibits erosive joint destruction and lowers inflammation but has no effect on bone formation in the delayed-type hypersensitivity arthritis (DTHA) model",
abstract = "Background: The aims of the present study were to determine the relationship between bone destruction and bone formation in the delayed-type hypersensitivity arthritis (DTHA) model and to evaluate the effect of receptor activator of nuclear factor kappa B ligand (RANKL) blockade on severity of arthritis, bone destruction, and bone formation. Methods: DTHA was induced in C57BL/6 mice. Inflammation, erosive joint damage, and new bone formation were semiquantitatively scored by histology. Osteoclast activity was assessed in vivo, and messenger RNA (mRNA) expression of mediators of bone destruction and bone formation were analyzed by mRNA deep sequencing. Serum concentrations of tartrate-resistant acid phosphatase 5b, carboxy-terminal telopeptide I (CTX-I), matrix metalloproteinase 3 (MMP3), and serum amyloid P component (SAP) were determined by enzyme-linked immunosorbent assay. Anti-RANKL monoclonal antibody treatment was initiated at the time of immunization. Results: Bone destruction (MMP3 serum levels, cathepsin B activity, and RANKL mRNA) peaked at day 3 after arthritis induction, followed by a peak in cartilage destruction and bone erosion on day 5 after arthritis induction. Periarticular bone formation was observed from day 10. Induction of new bone formation indicated by enhanced Runx2, collagen X, osteocalcin, MMP2, MMP9, and MMP13 mRNA expression was observed only between days 8 and 11. Anti-RANKL treatment resulted in a modest reduction in paw and ankle swelling and a reduction of serum levels of SAP, MMP3, and CTX-I. Destruction of the subchondral bone was significantly reduced, while no effect on bone formation was seen. Conclusions: Anti-RANKL treatment prevents joint destruction but does not prevent new bone formation in the DTHA model. Thus, although occurring sequentially during the course of DTHA, bone destruction and bone formation are apparently not linked in this model.",
keywords = "Arthritis, Joint inflammation, Bone destruction, Bone formation, Osteoclast, RANKL",
author = "Atkinson, {Sara Marie} and Janine Bleil and Rene Maier and Kuehl, {Anja A.} and Mette Thorn and Kyle Serikawa and Brian Fox and Kim Kruse and Claus Haase and Soren Skov and Anneline Nansen and Uta Syrbe",
year = "2016",
month = jan,
day = "23",
doi = "10.1186/s13075-016-0931-3",
language = "English",
volume = "18",
journal = "Arthritis Research & Therapy",
issn = "1478-6354",
publisher = "BioMed Central",

}

RIS

TY - JOUR

T1 - Anti-RANKL treatment inhibits erosive joint destruction and lowers inflammation but has no effect on bone formation in the delayed-type hypersensitivity arthritis (DTHA) model

AU - Atkinson, Sara Marie

AU - Bleil, Janine

AU - Maier, Rene

AU - Kuehl, Anja A.

AU - Thorn, Mette

AU - Serikawa, Kyle

AU - Fox, Brian

AU - Kruse, Kim

AU - Haase, Claus

AU - Skov, Soren

AU - Nansen, Anneline

AU - Syrbe, Uta

PY - 2016/1/23

Y1 - 2016/1/23

N2 - Background: The aims of the present study were to determine the relationship between bone destruction and bone formation in the delayed-type hypersensitivity arthritis (DTHA) model and to evaluate the effect of receptor activator of nuclear factor kappa B ligand (RANKL) blockade on severity of arthritis, bone destruction, and bone formation. Methods: DTHA was induced in C57BL/6 mice. Inflammation, erosive joint damage, and new bone formation were semiquantitatively scored by histology. Osteoclast activity was assessed in vivo, and messenger RNA (mRNA) expression of mediators of bone destruction and bone formation were analyzed by mRNA deep sequencing. Serum concentrations of tartrate-resistant acid phosphatase 5b, carboxy-terminal telopeptide I (CTX-I), matrix metalloproteinase 3 (MMP3), and serum amyloid P component (SAP) were determined by enzyme-linked immunosorbent assay. Anti-RANKL monoclonal antibody treatment was initiated at the time of immunization. Results: Bone destruction (MMP3 serum levels, cathepsin B activity, and RANKL mRNA) peaked at day 3 after arthritis induction, followed by a peak in cartilage destruction and bone erosion on day 5 after arthritis induction. Periarticular bone formation was observed from day 10. Induction of new bone formation indicated by enhanced Runx2, collagen X, osteocalcin, MMP2, MMP9, and MMP13 mRNA expression was observed only between days 8 and 11. Anti-RANKL treatment resulted in a modest reduction in paw and ankle swelling and a reduction of serum levels of SAP, MMP3, and CTX-I. Destruction of the subchondral bone was significantly reduced, while no effect on bone formation was seen. Conclusions: Anti-RANKL treatment prevents joint destruction but does not prevent new bone formation in the DTHA model. Thus, although occurring sequentially during the course of DTHA, bone destruction and bone formation are apparently not linked in this model.

AB - Background: The aims of the present study were to determine the relationship between bone destruction and bone formation in the delayed-type hypersensitivity arthritis (DTHA) model and to evaluate the effect of receptor activator of nuclear factor kappa B ligand (RANKL) blockade on severity of arthritis, bone destruction, and bone formation. Methods: DTHA was induced in C57BL/6 mice. Inflammation, erosive joint damage, and new bone formation were semiquantitatively scored by histology. Osteoclast activity was assessed in vivo, and messenger RNA (mRNA) expression of mediators of bone destruction and bone formation were analyzed by mRNA deep sequencing. Serum concentrations of tartrate-resistant acid phosphatase 5b, carboxy-terminal telopeptide I (CTX-I), matrix metalloproteinase 3 (MMP3), and serum amyloid P component (SAP) were determined by enzyme-linked immunosorbent assay. Anti-RANKL monoclonal antibody treatment was initiated at the time of immunization. Results: Bone destruction (MMP3 serum levels, cathepsin B activity, and RANKL mRNA) peaked at day 3 after arthritis induction, followed by a peak in cartilage destruction and bone erosion on day 5 after arthritis induction. Periarticular bone formation was observed from day 10. Induction of new bone formation indicated by enhanced Runx2, collagen X, osteocalcin, MMP2, MMP9, and MMP13 mRNA expression was observed only between days 8 and 11. Anti-RANKL treatment resulted in a modest reduction in paw and ankle swelling and a reduction of serum levels of SAP, MMP3, and CTX-I. Destruction of the subchondral bone was significantly reduced, while no effect on bone formation was seen. Conclusions: Anti-RANKL treatment prevents joint destruction but does not prevent new bone formation in the DTHA model. Thus, although occurring sequentially during the course of DTHA, bone destruction and bone formation are apparently not linked in this model.

KW - Arthritis

KW - Joint inflammation

KW - Bone destruction

KW - Bone formation

KW - Osteoclast

KW - RANKL

U2 - 10.1186/s13075-016-0931-3

DO - 10.1186/s13075-016-0931-3

M3 - Journal article

C2 - 26801240

VL - 18

JO - Arthritis Research & Therapy

JF - Arthritis Research & Therapy

SN - 1478-6354

M1 - 28

ER -

ID: 165571097