MSC-based therapy mitigates wear particle-induced chronic inflammation and associated bone loss in mice

Wear particles from total joint arthroplasties (TJAs) induce chronic inflammation, macrophage infiltration and lead to bone loss by promoting bone destruction and inhibiting bone formation. Inhibition of particle-associated chronic inflammation and the associated bone loss is critical to the success and survivorship of TJAs. The purpose of this study is to test the hypothesis that polyethylene particle induced chronic inflammatory bone loss could be suppressed by local injection of NF-κB sensing Interleukin-4 (IL-4) over-expressing MSCs using the murine continuous polyethylene particle infusion model. The animal model was generated with continuous infusion of polyethylene particles into the intramedullary space of the femur for 6 weeks. Cells were locally injected into the intramedullary space 3 weeks after the primary surgery. Femurs were collected 6 weeks after the primary surgery. Micro-computational tomography (μCT), histochemical and immunohistochemical analyses were performed. Particle-infusion resulted in a prolonged pro-inflammatory M1 macrophage dominated phenotype and a decrease of the anti-inflammatory M2 macrophage phenotype, an increase in TRAP positive osteoclasts, and lower alkaline phosphatase staining area and bone mineral density, indicating chronic particle-associated inflammatory bone loss. Local injection of MSCs or NF-κB sensing IL-4 over-expressing MSCs reversed the particle-associated chronic inflammatory bone loss and facilitated bone healing. These results demonstrated that local inflammatory bone loss can be effectively modulated via MSC-based treatments, which could be an efficacious therapeutic strategy for periprosthetic osteolysis.

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Emerging and future therapies for the treatment of bone loss associated with chronic inflammation

Inflammopharmacology ◽

10.1007/s10787-006-0006-1 ◽

2006 ◽

Vol 14 (5-6) ◽

pp. 193-197 ◽

Cited By ~ 14

Author(s):

D. R. Haynes

Keyword(s):

Bone Loss ◽

Chronic Inflammation

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Effect of green tea polyphenols on chronic inflammation‐induced bone loss in female rats

The FASEB Journal ◽

10.1096/fasebj.22.1_supplement.314.3 ◽

2008 ◽

Vol 22 (S1) ◽

Author(s):

Chwan‐Li Shen ◽

James K. Yeh ◽

Xiao‐Qing Liu ◽

Dale M Dunn ◽

Barbara J Stoecker ◽

...

Keyword(s):

Bone Loss ◽

Chronic Inflammation ◽

Green Tea ◽

Tea Polyphenols ◽

Female Rats ◽

Green Tea Polyphenols

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021 Therapeutic glucocorticoids prevent local and systemic bone loss but exacerbate muscle wasting when administered in chronic inflammation

Rheumatology ◽

10.1093/rheumatology/kez106.020 ◽

2019 ◽

Vol 58 (Supplement_3) ◽

Author(s):

Chloe G Fenton ◽

Justine Webster ◽

Syeda Fareed ◽

Claire Martin ◽

Corinna Wehmeyer ◽

...

Keyword(s):

Bone Loss ◽

Chronic Inflammation ◽

Muscle Wasting ◽

Systemic Bone Loss

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Resolution of Anterior Scleritis after Periodontal Therapy

European Journal of Dentistry ◽

10.1055/s-0039-1698901 ◽

2011 ◽

Vol 05 (03) ◽

pp. 337-339 ◽

Cited By ~ 2

Author(s):

Guliz Nigar Guncu ◽

Feriha Caglayan

Keyword(s):

Drug Reaction ◽

Bone Loss ◽

Chronic Inflammation ◽

Chronic Periodontitis ◽

Periodontal Therapy ◽

Rapid Resolution ◽

Immune Mediated ◽

Anterior Scleritis ◽

Inflammatory Drugs ◽

Topical Medications

ABSTRACTScleritis is a chronic inflammation that involves the outermost coat and the skeleton of the eye. Scleritis may be associated with a systemic or immune mediated disease and it might be caused by an infection, trauma or drug reaction. This case presents a patient with generalized chronic periodontitis and anterior diffuse scleritis. A 30-year-old female complained of pain and persistent scleritis in the left eye was referred to the Periodontology department due to her periodontal problems. She was treated with oral non steroidal anti-inflammatory drugs and topical medications (corticosteroid) for her scleritis during last two years. However, these treatments failed to control the progression of the disease. After periodontal examination, deep periodontal pockets and serious bone loss was detected radiographically. She was treated by flap procedures and 3 teeth were extracted. After a 4-month healing period, scleritis was resulted in rapid resolution. (Eur J Dent 2011;5:337-339)

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Glucocorticoids activation by 11beta-hydroxysteroid dehydrogenase type 1 protects against inflammatory bone loss in a murine model of chronic inflammation

Endocrine Abstracts ◽

10.1530/endoabs.50.oc6.2 ◽

2017 ◽

Author(s):

Rowan Hardy ◽

Chloe Fenton ◽

Rumina Begum ◽

Amy Naylor ◽

Atif Saghir ◽

...

Keyword(s):

Bone Loss ◽

Chronic Inflammation ◽

Murine Model ◽

Hydroxysteroid Dehydrogenase

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Is bone loss linked to chronic inflammation in antiretroviral-naive HIV-infected adults? A 48-week matched cohort study

AIDS ◽

10.1097/qad.0000000000000320 ◽

2014 ◽

Vol 28 (12) ◽

pp. 1759-1767 ◽

Cited By ~ 44

Author(s):

Corrilynn O. Hileman ◽

Danielle E. Labbato ◽

Norma J. Storer ◽

Vin Tangpricha ◽

Grace A. McComsey

Keyword(s):

Cohort Study ◽

Bone Loss ◽

Chronic Inflammation ◽

Matched Cohort ◽

Matched Cohort Study

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Omnipresence of inflammasome activities in inflammatory bone diseases

Seminars in Immunopathology ◽

10.1007/s00281-019-00753-4 ◽

2019 ◽

Vol 41 (5) ◽

pp. 607-618 ◽

Cited By ~ 6

Author(s):

Yael Alippe ◽

Gabriel Mbalaviele

Keyword(s):

Bone Resorption ◽

Bone Loss ◽

Chronic Inflammation ◽

Acute Inflammation ◽

Protein Complexes ◽

Bone Diseases ◽

Tissue Homeostasis ◽

Intracellular Protein ◽

Over Time

Abstract The inflammasomes are intracellular protein complexes that are assembled in response to a variety of perturbations including infections and injuries. Failure of the inflammasomes to rapidly clear the insults or restore tissue homeostasis can result in chronic inflammation. Recurring inflammation is also provoked by mutations that cause the constitutive assembly of the components of these protein platforms. Evidence suggests that chronic inflammation is a shared mechanism in bone loss associated with aging, dysregulated metabolism, autoinflammatory, and autoimmune diseases. Mechanistically, inflammatory mediators promote bone resorption while suppressing bone formation, an imbalance which over time leads to bone loss and increased fracture risk. Thus, while acute inflammation is important for the maintenance of bone integrity, its chronic state damages this tissue. In this review, we discuss the role of the inflammasomes in inflammation-induced osteolysis.

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Evidence for Gender-Specific Bone Loss Mechanisms in Periprosthetic Osteolysis

Journal of Clinical Medicine ◽

10.3390/jcm9010053 ◽

2019 ◽

Vol 9 (1) ◽

pp. 53 ◽

Cited By ~ 2

Author(s):

Renee T. Ormsby ◽

Lucian B. Solomon ◽

Roumen Stamenkov ◽

David M. Findlay ◽

Gerald J. Atkins

Keyword(s):

Bone Resorption ◽

Bone Loss ◽

Wear Particle ◽

Wear Particles ◽

Periprosthetic Osteolysis ◽

Osteocyte Lacunae ◽

Patient Gender ◽

Bone Biopsies ◽

Numerous Cell ◽

Gender Specific

Osteolysis adjacent to total hip replacement (THR) prostheses is a major cause of their eventual failure. Periprosthetic osteolysis is associated with the production of bioactive particles, produced by the wear of articulating prosthesis surfaces. Wear particles invade the periprosthetic tissue, inducing inflammation and bone resorption. Previous studies have shown that osteocytes, the most numerous cell type in mineralised bone, can respond to wear particles of multiple orthopaedic material types. Osteocytes play important roles in bone resorption, regulating bone resorption by osteoclasts and directly through osteocytic osteolysis, also known as perilacunar remodelling. In this study, we perform a histological analysis of bone biopsies obtained from cohorts of male and female patients undergoing either primary THR surgery or revision THR surgery for aseptic loosening. The osteocyte lacunae area (Ot.Lac.Ar) and percentage lacunar area/bone area (%Ot.Lac.Ar/B.Ar) were significantly larger overall in revision THR bone than bone from similar sites in primary THR. Analysis by patient gender showed that increased Ot.Lac.Ar, indicative of increased perilacunar remodelling, was restricted to female revision samples. No significant differences in osteoclast parameters were detectable between the cohorts. These findings suggest previously unrecognised gender-specific mechanisms of bone loss in orthopaedic wear particle-induced osteolysis in humans.

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