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A model of inflammatory arthritis highlights a role for oncostatin M in pro-inflammatory cytokine-induced bone destruction via RANK/RANKL.

Hui W, Cawston TE, Richards CD, Rowan AD - Arthritis Res. Ther. (2004)

Bottom Line: However, the in vivo effects of these potent cytokine combinations on bone catabolism are unknown.Furthermore, there was increased expression of RANK and its ligand RANKL in the inflammatory cells, in inflamed synovium and in articular cartilage of knee joints treated with the cytokine combinations compared with expression in joints treated with the cytokines alone or the control.The model also provides further evidence that increased osteoclast-like, tartrate-resistant acid phosphatase-positive staining multinucleate cells and upregulation of RANK/RANKL in joint tissues are key factors in pathological bone destruction.

View Article: PubMed Central - HTML - PubMed

Affiliation: Musculoskeletal Research Group, The Medical School, University of Newcastle, Newcastle upon Tyne, UK. wang.hui@ncl.ac.uk

ABSTRACT
Oncostatin M is a pro-inflammatory cytokine previously shown to promote marked cartilage destruction both in vitro and in vivo when in combination with IL-1 or tumour necrosis factor alpha. However, the in vivo effects of these potent cytokine combinations on bone catabolism are unknown. Using adenoviral gene transfer, we have overexpressed oncostatin M in combination with either IL-1 or tumour necrosis factor alpha intra-articularly in the knees of C57BL/6 mice. Both of these combinations induced marked bone damage and markedly increased tartrate-resistant acid phosphatase-positive multinucleate cell staining in the synovium and at the front of bone erosions. Furthermore, there was increased expression of RANK and its ligand RANKL in the inflammatory cells, in inflamed synovium and in articular cartilage of knee joints treated with the cytokine combinations compared with expression in joints treated with the cytokines alone or the control. This model of inflammatory arthritis demonstrates that, in vivo, oncostatin M in combination with either IL-1 or tumour necrosis factor alpha represents cytokine combinations that promote bone destruction. The model also provides further evidence that increased osteoclast-like, tartrate-resistant acid phosphatase-positive staining multinucleate cells and upregulation of RANK/RANKL in joint tissues are key factors in pathological bone destruction.

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Bone damage caused by oncostatin M (OSM) in combination with either IL-1 or tumour necrosis factor alpha (TNF-α) in murine joints. Adenovirus vectors overexpressing murine OSM, IL-1 or TNF-α were injected intra-articularly into the right knee joints of mice at 5 × 106 plaque-forming units [pfu]/vector/joint. The left knee joints were injected with the empty control vector. All joints received a total of 1 × 107 pfu/joint, and all animals were sacrificed at day 7 following administration. Sections (5 μm) were stained with H&E. (a) Control, (b) OSM, (c) IL-1, (d) TNF-α, (e), (f) OSM + IL-1, and (g), (h) OSM + TNF-α. The joints showed a moderate (b–d) to severe (e–h) synovial hyperplasia and an infiltration of inflammatory cells. Marked synovial hyperplasia with angiogenesis was also seen with bone erosions (arrows) and bone fractures, with evidence of synovial invasion (e and g). b, bone; bm, bone marrow; f, bone fracture; m, muscle; s, synovial cells; v, blood vessel. (a)–(e), (g) Bar = 50 μm; (f), (h) bar = 20 μm.
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Figure 1: Bone damage caused by oncostatin M (OSM) in combination with either IL-1 or tumour necrosis factor alpha (TNF-α) in murine joints. Adenovirus vectors overexpressing murine OSM, IL-1 or TNF-α were injected intra-articularly into the right knee joints of mice at 5 × 106 plaque-forming units [pfu]/vector/joint. The left knee joints were injected with the empty control vector. All joints received a total of 1 × 107 pfu/joint, and all animals were sacrificed at day 7 following administration. Sections (5 μm) were stained with H&E. (a) Control, (b) OSM, (c) IL-1, (d) TNF-α, (e), (f) OSM + IL-1, and (g), (h) OSM + TNF-α. The joints showed a moderate (b–d) to severe (e–h) synovial hyperplasia and an infiltration of inflammatory cells. Marked synovial hyperplasia with angiogenesis was also seen with bone erosions (arrows) and bone fractures, with evidence of synovial invasion (e and g). b, bone; bm, bone marrow; f, bone fracture; m, muscle; s, synovial cells; v, blood vessel. (a)–(e), (g) Bar = 50 μm; (f), (h) bar = 20 μm.

Mentions: The morphology of H&E-stained sections from all treated joints (5 × 106 pfu/vector/joint) was assessed, and indicated that the contralateral joints treated with the control vector showed no evidence of bone damage (Fig. 1a). Administration of each cytokine alone caused a moderate synovial hyperplasia and bone erosions (Fig. 1b,1c,1d).


A model of inflammatory arthritis highlights a role for oncostatin M in pro-inflammatory cytokine-induced bone destruction via RANK/RANKL.

Hui W, Cawston TE, Richards CD, Rowan AD - Arthritis Res. Ther. (2004)

Bone damage caused by oncostatin M (OSM) in combination with either IL-1 or tumour necrosis factor alpha (TNF-α) in murine joints. Adenovirus vectors overexpressing murine OSM, IL-1 or TNF-α were injected intra-articularly into the right knee joints of mice at 5 × 106 plaque-forming units [pfu]/vector/joint. The left knee joints were injected with the empty control vector. All joints received a total of 1 × 107 pfu/joint, and all animals were sacrificed at day 7 following administration. Sections (5 μm) were stained with H&E. (a) Control, (b) OSM, (c) IL-1, (d) TNF-α, (e), (f) OSM + IL-1, and (g), (h) OSM + TNF-α. The joints showed a moderate (b–d) to severe (e–h) synovial hyperplasia and an infiltration of inflammatory cells. Marked synovial hyperplasia with angiogenesis was also seen with bone erosions (arrows) and bone fractures, with evidence of synovial invasion (e and g). b, bone; bm, bone marrow; f, bone fracture; m, muscle; s, synovial cells; v, blood vessel. (a)–(e), (g) Bar = 50 μm; (f), (h) bar = 20 μm.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1064887&req=5

Figure 1: Bone damage caused by oncostatin M (OSM) in combination with either IL-1 or tumour necrosis factor alpha (TNF-α) in murine joints. Adenovirus vectors overexpressing murine OSM, IL-1 or TNF-α were injected intra-articularly into the right knee joints of mice at 5 × 106 plaque-forming units [pfu]/vector/joint. The left knee joints were injected with the empty control vector. All joints received a total of 1 × 107 pfu/joint, and all animals were sacrificed at day 7 following administration. Sections (5 μm) were stained with H&E. (a) Control, (b) OSM, (c) IL-1, (d) TNF-α, (e), (f) OSM + IL-1, and (g), (h) OSM + TNF-α. The joints showed a moderate (b–d) to severe (e–h) synovial hyperplasia and an infiltration of inflammatory cells. Marked synovial hyperplasia with angiogenesis was also seen with bone erosions (arrows) and bone fractures, with evidence of synovial invasion (e and g). b, bone; bm, bone marrow; f, bone fracture; m, muscle; s, synovial cells; v, blood vessel. (a)–(e), (g) Bar = 50 μm; (f), (h) bar = 20 μm.
Mentions: The morphology of H&E-stained sections from all treated joints (5 × 106 pfu/vector/joint) was assessed, and indicated that the contralateral joints treated with the control vector showed no evidence of bone damage (Fig. 1a). Administration of each cytokine alone caused a moderate synovial hyperplasia and bone erosions (Fig. 1b,1c,1d).

Bottom Line: However, the in vivo effects of these potent cytokine combinations on bone catabolism are unknown.Furthermore, there was increased expression of RANK and its ligand RANKL in the inflammatory cells, in inflamed synovium and in articular cartilage of knee joints treated with the cytokine combinations compared with expression in joints treated with the cytokines alone or the control.The model also provides further evidence that increased osteoclast-like, tartrate-resistant acid phosphatase-positive staining multinucleate cells and upregulation of RANK/RANKL in joint tissues are key factors in pathological bone destruction.

View Article: PubMed Central - HTML - PubMed

Affiliation: Musculoskeletal Research Group, The Medical School, University of Newcastle, Newcastle upon Tyne, UK. wang.hui@ncl.ac.uk

ABSTRACT
Oncostatin M is a pro-inflammatory cytokine previously shown to promote marked cartilage destruction both in vitro and in vivo when in combination with IL-1 or tumour necrosis factor alpha. However, the in vivo effects of these potent cytokine combinations on bone catabolism are unknown. Using adenoviral gene transfer, we have overexpressed oncostatin M in combination with either IL-1 or tumour necrosis factor alpha intra-articularly in the knees of C57BL/6 mice. Both of these combinations induced marked bone damage and markedly increased tartrate-resistant acid phosphatase-positive multinucleate cell staining in the synovium and at the front of bone erosions. Furthermore, there was increased expression of RANK and its ligand RANKL in the inflammatory cells, in inflamed synovium and in articular cartilage of knee joints treated with the cytokine combinations compared with expression in joints treated with the cytokines alone or the control. This model of inflammatory arthritis demonstrates that, in vivo, oncostatin M in combination with either IL-1 or tumour necrosis factor alpha represents cytokine combinations that promote bone destruction. The model also provides further evidence that increased osteoclast-like, tartrate-resistant acid phosphatase-positive staining multinucleate cells and upregulation of RANK/RANKL in joint tissues are key factors in pathological bone destruction.

Show MeSH
Related in: MedlinePlus