Expression of osteoclast differentiation factor at sites of bone erosion in collagen-induced arthritis

Evan Romas, Olga Bakharevski, Daphne K. Hards, Vicky Kartsogiannis, Julian M W Quinn, Peter F J Ryan, T. John Martin, Matthew T. Gillespie

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Objective. To investigate the cellular mechanism of bone destruction in collagen-induced arthritis (CIA). Methods. After induction of CIA in DA rats, a histologic study of the advanced arthritic lesion was carried out on whole, decalcified joints from the hindpaws of affected animals. To conclusively identify osteoclasts, joint tissue sections were stained for tartrateresistant acid phosphatase (TRAP) enzyme activity, and calcitonin receptors (CTR) were identified using a specific rabbit polyclonal antibody. The expression of messenger RNA (mRNA) for the osteoclast differentiation factor (also known as receptor activator of nuclear factor κB ligand [RANKL]) was investigated using in situ hybridization with a specific riboprobe. Results. TRAP-positive and CTR-positive multinucleated cells were invariably detected in arthritic lesions that were characterized by bone destruction. Osteoclasts were identified at the pannus-bone and pannus-subchondral bone junctions of arthritic joints, where they formed erosive pits in the bone. TRAP-positive multinucleated cells were detected within synovium and at the bone erosive front; however, CTR-positive multinucleated cells were present only at sites adjacent to bone. RANKL mRNA was highly expressed in the synovial cell infiltrate in arthritic joints, as well as by osteoclasts at sites of bone erosion. Conclusion. Focal bone erosion in CIA is attributed to cells expressing definitive features of osteoclasts, including CTR. The expression of RANKL by cells within inflamed synovium suggests a mechanism for osteoclast differentiation and activation at sites of bone erosion. Inhibitors of RANKL may represent a novel approach to treatment of bone loss in rheumatoid arthritis.

Original languageEnglish
Pages (from-to)821-826
Number of pages6
JournalArthritis and Rheumatism
Volume43
Issue number4
DOIs
Publication statusPublished - 18 Sep 2000

Cite this

Romas, Evan ; Bakharevski, Olga ; Hards, Daphne K. ; Kartsogiannis, Vicky ; Quinn, Julian M W ; Ryan, Peter F J ; Martin, T. John ; Gillespie, Matthew T. / Expression of osteoclast differentiation factor at sites of bone erosion in collagen-induced arthritis. In: Arthritis and Rheumatism. 2000 ; Vol. 43, No. 4. pp. 821-826.
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abstract = "Objective. To investigate the cellular mechanism of bone destruction in collagen-induced arthritis (CIA). Methods. After induction of CIA in DA rats, a histologic study of the advanced arthritic lesion was carried out on whole, decalcified joints from the hindpaws of affected animals. To conclusively identify osteoclasts, joint tissue sections were stained for tartrateresistant acid phosphatase (TRAP) enzyme activity, and calcitonin receptors (CTR) were identified using a specific rabbit polyclonal antibody. The expression of messenger RNA (mRNA) for the osteoclast differentiation factor (also known as receptor activator of nuclear factor κB ligand [RANKL]) was investigated using in situ hybridization with a specific riboprobe. Results. TRAP-positive and CTR-positive multinucleated cells were invariably detected in arthritic lesions that were characterized by bone destruction. Osteoclasts were identified at the pannus-bone and pannus-subchondral bone junctions of arthritic joints, where they formed erosive pits in the bone. TRAP-positive multinucleated cells were detected within synovium and at the bone erosive front; however, CTR-positive multinucleated cells were present only at sites adjacent to bone. RANKL mRNA was highly expressed in the synovial cell infiltrate in arthritic joints, as well as by osteoclasts at sites of bone erosion. Conclusion. Focal bone erosion in CIA is attributed to cells expressing definitive features of osteoclasts, including CTR. The expression of RANKL by cells within inflamed synovium suggests a mechanism for osteoclast differentiation and activation at sites of bone erosion. Inhibitors of RANKL may represent a novel approach to treatment of bone loss in rheumatoid arthritis.",
author = "Evan Romas and Olga Bakharevski and Hards, {Daphne K.} and Vicky Kartsogiannis and Quinn, {Julian M W} and Ryan, {Peter F J} and Martin, {T. John} and Gillespie, {Matthew T.}",
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Expression of osteoclast differentiation factor at sites of bone erosion in collagen-induced arthritis. / Romas, Evan; Bakharevski, Olga; Hards, Daphne K.; Kartsogiannis, Vicky; Quinn, Julian M W; Ryan, Peter F J; Martin, T. John; Gillespie, Matthew T.

In: Arthritis and Rheumatism, Vol. 43, No. 4, 18.09.2000, p. 821-826.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Expression of osteoclast differentiation factor at sites of bone erosion in collagen-induced arthritis

AU - Romas, Evan

AU - Bakharevski, Olga

AU - Hards, Daphne K.

AU - Kartsogiannis, Vicky

AU - Quinn, Julian M W

AU - Ryan, Peter F J

AU - Martin, T. John

AU - Gillespie, Matthew T.

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N2 - Objective. To investigate the cellular mechanism of bone destruction in collagen-induced arthritis (CIA). Methods. After induction of CIA in DA rats, a histologic study of the advanced arthritic lesion was carried out on whole, decalcified joints from the hindpaws of affected animals. To conclusively identify osteoclasts, joint tissue sections were stained for tartrateresistant acid phosphatase (TRAP) enzyme activity, and calcitonin receptors (CTR) were identified using a specific rabbit polyclonal antibody. The expression of messenger RNA (mRNA) for the osteoclast differentiation factor (also known as receptor activator of nuclear factor κB ligand [RANKL]) was investigated using in situ hybridization with a specific riboprobe. Results. TRAP-positive and CTR-positive multinucleated cells were invariably detected in arthritic lesions that were characterized by bone destruction. Osteoclasts were identified at the pannus-bone and pannus-subchondral bone junctions of arthritic joints, where they formed erosive pits in the bone. TRAP-positive multinucleated cells were detected within synovium and at the bone erosive front; however, CTR-positive multinucleated cells were present only at sites adjacent to bone. RANKL mRNA was highly expressed in the synovial cell infiltrate in arthritic joints, as well as by osteoclasts at sites of bone erosion. Conclusion. Focal bone erosion in CIA is attributed to cells expressing definitive features of osteoclasts, including CTR. The expression of RANKL by cells within inflamed synovium suggests a mechanism for osteoclast differentiation and activation at sites of bone erosion. Inhibitors of RANKL may represent a novel approach to treatment of bone loss in rheumatoid arthritis.

AB - Objective. To investigate the cellular mechanism of bone destruction in collagen-induced arthritis (CIA). Methods. After induction of CIA in DA rats, a histologic study of the advanced arthritic lesion was carried out on whole, decalcified joints from the hindpaws of affected animals. To conclusively identify osteoclasts, joint tissue sections were stained for tartrateresistant acid phosphatase (TRAP) enzyme activity, and calcitonin receptors (CTR) were identified using a specific rabbit polyclonal antibody. The expression of messenger RNA (mRNA) for the osteoclast differentiation factor (also known as receptor activator of nuclear factor κB ligand [RANKL]) was investigated using in situ hybridization with a specific riboprobe. Results. TRAP-positive and CTR-positive multinucleated cells were invariably detected in arthritic lesions that were characterized by bone destruction. Osteoclasts were identified at the pannus-bone and pannus-subchondral bone junctions of arthritic joints, where they formed erosive pits in the bone. TRAP-positive multinucleated cells were detected within synovium and at the bone erosive front; however, CTR-positive multinucleated cells were present only at sites adjacent to bone. RANKL mRNA was highly expressed in the synovial cell infiltrate in arthritic joints, as well as by osteoclasts at sites of bone erosion. Conclusion. Focal bone erosion in CIA is attributed to cells expressing definitive features of osteoclasts, including CTR. The expression of RANKL by cells within inflamed synovium suggests a mechanism for osteoclast differentiation and activation at sites of bone erosion. Inhibitors of RANKL may represent a novel approach to treatment of bone loss in rheumatoid arthritis.

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