WEAR DEBRIS INHIBITION OF ANTI-OSTEOCLASTOGENIC SIGNALING BY INTERLEUKIN-6 AND INTERFERON-γ

Rakshit, Diptendu S.; Ly, Khanh; Sengupta, Tapas K.; Nestor, Bryan J.; Sculco, Thomas P.; Ivashkiv, Lionel B.; Purdue, P. Edward

doi:10.2106/00004623-200604000-00014

Cited by 3 publications

(4 citation statements)

References 38 publications

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“…It is well-known that the occurrence of aseptic periprosthetic osteolysis involves several kinds of cells such as macrophages, osteoblasts, T lymphocytes, and multinucleated osteoclasts. 36 Recent studies have demonstrated that immune and skeletal systems show a series of signaling crosstalk. 37 The close relationship between immune and skeletal systems suggests the significance of immune cells in modulating osteocytes.…”

Section: Discussionmentioning

confidence: 99%

MgO Nanoparticles Protect against Titanium Particle-Induced Osteolysis in a Mouse Model Because of Their Positive Immunomodulatory Effect

Yin

Huang

Yang

et al. 2020

ACS Biomater. Sci. Eng.

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Aseptic prosthetic loosening (APL) often leads to the failure of prostheses. It is inseparable from wear-particle-induced macrophage-mediated inflammatory responses and osteolysis. Mg2+ is a metal ion with excellent anti-inflammatory properties. Herein, Mg2+ was introduced into a nanomedicine (MgO nanoparticles (MNPs)) to protect against APL. MNPs could be phagocytized by macrophages and gradually degraded intracellularly. Following MNPs treatment, lipopolysaccharide (LPS)-activated macrophages polarized into deeper M1 phenotype at 6 h but then switched to the M2 phenotype at 48 h. Furthermore, the MNPs suppressed the titanium (Ti) particle-induced osteoclastogenesis and osteolysis in vivo. However, the MNPs exhibited no impact on the receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis and even inhibited osteogenesis in vitro. The contrary results between the in vitro and in vivo experiments imply that macrophages are the key factor in the inhibited osteoclastogenesis in vivo because the pathogenic process of APL is mainly attributed to macrophages, osteoblasts, and osteoclasts. Accordingly, an indirect coculture system was designed that considers the immunomodulatory effect of macrophages. RANKL-induced osteoclastogenesis was significantly inhibited under the influence of MNPs in the indirect coculture system. Taken together, the MNPs inhibited the inflammatory responses of macrophages provoked by the Ti particles and thus regulated the expressions of RANKL and OPG in osteoblasts to suppress osteoclastogenesis. The target cell of MNPs was macrophages but not osteoclasts, indicating the importance of the immunomodulatory effect of macrophages. These results collectively demonstrated that MNPs can prevent APL and other osteolysis-related diseases.

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Section: Discussionmentioning

confidence: 99%

MgO Nanoparticles Protect against Titanium Particle-Induced Osteolysis in a Mouse Model Because of Their Positive Immunomodulatory Effect

Yin

Huang

Yang

et al. 2020

ACS Biomater. Sci. Eng.

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“…The inflammatory response to wear debris is an important factor in the development of periprosthetic osteolysis. It was confirmed that polymethylmethacrylate and titanium significantly inhibited IL-6-induced STAT3 activation in osteoclast precursors, suggesting that the mechanism of wear debris in periprosthetic osteolysis may be through the inhibition of anti-osteoclastogenic cytokine signalling [ 100 ] (Table 3 ; Fig. 4 ).…”

Section: Stat3 Signalling Pathway and Osteoclastogenesismentioning

confidence: 93%

STAT3-mediated osteogenesis and osteoclastogenesis in osteoporosis

Hou

Tian

2022

Cell Commun Signal

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Osteoporosis is a common skeletal disease with marked bone loss, deterioration of the bone microstructure and bone fragility. An abnormal bone remodelling cycle with relatively increased bone resorption is the crucial pathophysiological mechanism. Bone remodelling is predominantly controlled by osteoblasts and osteoclasts, which are specialized cell types that are regulated by a variety of osteogenic and osteoclastic factors, including cytokines expressed within the bone microenvironment under local or systemic inflammatory conditions. Signal transducer and activator of transcription 3 (STAT3) plays a prominent role in the communication between cytokines and kinases by binding downstream gene promotors and is involved in a wide range of biological or pathological processes. Emerging evidence suggests that STAT3 and its network participate in bone remodelling and the development of osteoporosis, and this factor may be a potent target for osteoporosis treatment. This review focuses on the role and molecular mechanism of the STAT3 signalling pathway in osteogenesis, osteoclastogenesis and osteoporosis, particularly the bone-related cytokines that regulate the osteoblastic differentiation of bone marrow stromal cells and the osteoclastic differentiation of bone marrow macrophages by initiating STAT3 signalling. This review also examines the cellular interactions among immune cells, haematopoietic cells and osteoblastic/osteoclastic cells.

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“…Human osteoclast precursor cells exposed to titanium or PMMA particles in vitro induced MAP kinase activation; inhibition of MAP kinase activity suppressed pro-inammatory cytokine expression. 63 In this section, the biological roles of the cells in response to wear particles and disease progression are summarized.…”

Section: C3 Cellular and Molecular Biology Of The Implant Interfacementioning

confidence: 99%

“…Wear particles can generate the inltration of osteoclast precursor cells into functional osteoclasts via indirect effects from cytokines secreted from cells in the interface region, 62,63 or by direct activation of the precursor cells. In vitro studies have shown that wear particles can either suppress the cytokines with antiosteoclastogenesis function (interferon-g and IL-6), 63 or enhance the expression of TNF-a and IL-1b that activate bone resorption. 62 In addition, functional osteoclasts can be activated via the RANK/ RANKL pathway.…”

Section: C3 Cellular and Molecular Biology Of The Implant Interfacementioning

confidence: 99%

Interaction of materials and biology in total joint replacement – successes, challenges and future directions

et al. 2014

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Total joint replacement (TJR) has revolutionized the treatment of end-stage arthritic disorders. This success is due, in large part, to a clear understanding of the important interaction between the artificial implant and the biology of the host. All surgical procedures in which implants are placed in the body evoke an initial inflammatory reaction, which generally subsides over several weeks. Thereafter, a series of homeostatic events occur leading to progressive integration of the implant within bone and the surrounding musculoskeletal tissues. The eventual outcome of the operation is dependent on the characteristics of the implant, the precision of the surgical technique and operative environment, and the biological milieu of the host. If these factors and events are not optimal, adverse events can occur such as the development of chronic inflammation, progressive bone loss due to increased production of degradation products from the implant (periprosthetic osteolysis), implant loosening or infection. These complications can lead to chronic pain and poor function of the joint reconstruction, and may necessitate revision surgery or removal of the prosthesis entirely. Recent advances in engineering, materials science, and the immunological aspects associated with orthopaedic implants have fostered intense research with the hope that joint replacements will last a lifetime, and facilitate pain-free, normal function.

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WEAR DEBRIS INHIBITION OF ANTI-OSTEOCLASTOGENIC SIGNALING BY INTERLEUKIN-6 AND INTERFERON-γ

Cited by 3 publications

References 38 publications

MgO Nanoparticles Protect against Titanium Particle-Induced Osteolysis in a Mouse Model Because of Their Positive Immunomodulatory Effect

MgO Nanoparticles Protect against Titanium Particle-Induced Osteolysis in a Mouse Model Because of Their Positive Immunomodulatory Effect

STAT3-mediated osteogenesis and osteoclastogenesis in osteoporosis

Interaction of materials and biology in total joint replacement – successes, challenges and future directions

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