The plasminogen activation system is upregulated in loosening of total hip prostheses

Nordsletten, Lars; Buø, Laila; Takagi, Michiaki; Konttinen, Yrjö T.; Yamakawa, Mitsunori; Santavirta, Seppo; Aasen, Ansgar O.

doi:10.3109/17453679608994659

Cited by 10 publications

(9 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The localised release of chemokines may contribute to the formation of the synovial-like membrane described in aseptic loosening. 29 The synovial-like membrane shows increased levels of profibrotic and immunosuppressive transforming growth factor-ß 29 and upregulation of the plasminogen activation system, 30 which are consistent with a chronic inflammatory response. Our chemotactic studies confirm that particle-induced chemokine release from monocytes/macrophages increases monocyte migration across a membrane.…”

Section: Discussionmentioning

confidence: 66%

Induction of macrophage C-C chemokine expression by titanium alloy and bone cement particles

Nakashima

Sun

Trindade

et al. 1999

The Journal of Bone and Joint Surgery. British volume

View full text Add to dashboard Cite

Particulate wear debris is associated with periprosthetic inflammation and loosening in total joint arthroplasty. We tested the effects of titanium alloy (Ti-alloy) and PMMA particles on monocyte/macrophage expression of the C-C chemokines, monocyte chemoattractant protein-1 (MCP-1), monocyte inflammatory protein-1 alpha (MIP-1␣), and regulated upon activation normal T expressed and secreted protein (RANTES). Periprosthetic granulomatous tissue was analysed for expression of macrophage chemokines by immunohistochemistry. Chemokine expression in human monocytes/macrophages exposed to Ti-alloy and PMMA particles in vitro was determined by RT-PCR, ELISA and monocyte migration.We observed MCP-1 and MIP-1␣ expression in all tissue samples from failed arthroplasties. Ti-alloy and PMMA particles increased expression of MCP-1 and MIP-1␣ in macrophages in vitro in a dose-and time-dependent manner whereas RANTES was not detected. mRNA signal levels for MCP-1 and MIP-1␣ were also observed in cells after exposure to particles. Monocyte migration was stimulated by culture medium collected from macrophages exposed to Ti-alloy and PMMA particles. Antibodies to MCP-1 and MIP-1␣ inhibited chemotactic activity of the culture medium samples.Release of C-C chemokines by macrophages in response to wear particles may contribute to chronic inflammation at the bone-implant interface in total joint arthroplasty.J Bone Joint Surg [Br] 1999;81-B:155-62.

show abstract

Section: Discussionmentioning

confidence: 66%

Induction of macrophage C-C chemokine expression by titanium alloy and bone cement particles

Nakashima

Sun

Trindade

et al. 1999

The Journal of Bone and Joint Surgery. British volume

View full text Add to dashboard Cite

show abstract

“…Immunohistochemical study of the plasminogen activation system, which is closely associated with MMP activities, disclosed localization in periprosthetic tissues of urokinase plasminogen activator (uPA), uPA-receptor (uPAR), and tissue type plasminogen activator (tPA) in macrophages with phagocytosed metal, polyethylene, cement particles, or accompanying pieces of necrotic bone [86]. Plasminogen activator inhibitor-1 (PAI-1) staining was present in the neighboring areas that stained for uPA or tPA, but PAI-1 staining was also found overlapping and outside these areas.…”

Section: Matrix Metalloproteinases Their Endogenous Tissue Inhibimentioning

confidence: 99%

Extracellular Matrix Degradation and Tissue Remodeling in Periprosthetic Loosening and Osteolysis: Focus on Matrix Metalloproteinases, Their Endogenous Tissue Inhibitors, and the Proteasome

Syggelos

Aletras

Smirlaki

et al. 2013

BioMed Research International

View full text Add to dashboard Cite

The leading complication of total joint replacement is periprosthetic osteolysis, which often results in aseptic loosening of the implant, leading to revision surgery. Extracellular matrix degradation and connective tissue remodeling around implants have been considered as major biological events in the periprosthetic loosening. Critical mediators of wear particle-induced inflammatory osteolysis released by periprosthetic synovial cells (mainly macrophages) are inflammatory cytokines, chemokines, and proteolytic enzymes, mainly matrix metalloproteinases (MMPs). Numerous studies reveal a strong interdependence of MMP expression and activity with the molecular mechanisms that control the composition and turnover of periprosthetic matrices. MMPs can either actively modulate or be modulated by the molecular mechanisms that determine the debris-induced remodeling of the periprosthetic microenvironment. In the present study, the molecular mechanisms that control the composition, turnover, and activity of matrix macromolecules within the periprosthetic microenvironment exposed to wear debris are summarized and presented. Special emphasis is given to MMPs and their endogenous tissue inhibitors (TIMPs), as well as to the proteasome pathway, which appears to be an elegant molecular regulator of specific matrix macromolecules (including specific MMPs and TIMPs). Furthermore, strong rationale for potential clinical applications of the described molecular mechanisms to the treatment of periprosthetic loosening and osteolysis is provided.

show abstract

“…Macrophages activated by the phagocytosed wear particles can produce proteolytic and fibrinolytic enzymes, such as tissue plasminogen activator (Nordsletten et al 1996). We therefore studied the clotting and the fibrinolytic pathways in patients having loose prostheses to determine whether systemic changes occurred, even at a subclinical level.…”

Section: Discussionmentioning

confidence: 99%

“…It has been thought that fibrinolysis may play a role in extracellular matrix degradation in periprosthetic tissues. Macrophages containing phagocytosed material express plasminogen activators, which suggests that undegradable microdebris can initiate and perpetuate a proteolytic activation cascade (Nordsletten et al 1996). Plasminogen activators, together with other serine proteinases and metalloproteinases, have been found in the interface and pseudocapsular tissues (Takagi 1996).…”

mentioning

confidence: 99%

Plasma levels of coagulation inhibitors, fibrinolytic markers and platelet-derived growth factor-AB in patients with failed hip prosthesis

Cenni

Savarino

Baldini

et al. 2003

Acta Orthopaedica Scandinavica

View full text Add to dashboard Cite

The plasminogen activation system is upregulated in loosening of total hip prostheses

Cited by 10 publications

References 22 publications

Induction of macrophage C-C chemokine expression by titanium alloy and bone cement particles

Induction of macrophage C-C chemokine expression by titanium alloy and bone cement particles

Extracellular Matrix Degradation and Tissue Remodeling in Periprosthetic Loosening and Osteolysis: Focus on Matrix Metalloproteinases, Their Endogenous Tissue Inhibitors, and the Proteasome

Plasma levels of coagulation inhibitors, fibrinolytic markers and platelet-derived growth factor-AB in patients with failed hip prosthesis

Contact Info

Product

Resources

About