Distinct tribological endotypes of pathological human synovial fluid reveal characteristic biomarkers and variation in efficacy of viscosupplementation at reducing local strains in articular cartilage

R M Irwin; E Feeney; C Secchieri; D Galesso; I Cohen; F Oliviero; R Ramonda; L J Bonassar

doi:10.1016/j.joca.2020.02.029

Distinct tribological endotypes of pathological human synovial fluid reveal characteristic biomarkers and variation in efficacy of viscosupplementation at reducing local strains in articular cartilage

Osteoarthritis Cartilage. 2020 Apr;28(4):492-501. doi: 10.1016/j.joca.2020.02.029. Epub 2020 Feb 24.

Authors

R M Irwin¹, E Feeney², C Secchieri³, D Galesso⁴, I Cohen⁵, F Oliviero⁶, R Ramonda⁷, L J Bonassar⁸

Affiliations

¹ Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA. Electronic address: rmi8@cornell.edu.
² Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA. Electronic address: ef362@cornell.edu.
³ Fidia Farmaceutici S.p.A., Padua, Italy. Electronic address: cynthiasecchieri@gmail.com.
⁴ Fidia Farmaceutici S.p.A., Padua, Italy. Electronic address: DGalesso@fidiapharma.it.
⁵ Department of Physics, Cornell University, Ithaca, NY, USA. Electronic address: itai.cohen@cornell.edu.
⁶ Rheumatology Unit, Department of Medicine-DIMED, University of Padua, Padua, Italy. Electronic address: francesca.oliviero@unipd.it.
⁷ Rheumatology Unit, Department of Medicine-DIMED, University of Padua, Padua, Italy. Electronic address: roberta.ramonda@unipd.it.
⁸ Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA; Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, USA. Electronic address: lb244@cornell.edu.

Abstract

Objective: Viscosupplementation has been used for decades to treat mild to moderate osteoarthritis, yet it is unknown if the lubricating function of different pathological synovial fluids (SF) vary, or if they respond differentially to viscosupplementation. The objectives of this study were to (i) evaluate the friction coefficients and induced shear strains in articular cartilage when lubricated with pathological SF, (ii) identify the effect of hyaluronic acid (HA) supplementation on friction coefficients and shear strains, and (iii) identify SF biomarkers that correlate with lubricating function.

Method: Human pathological SF was grouped by white blood cell count (inflammatory: >2000 cells/mm³, n = 6; non-inflammatory: <2000 cells/mm³, n = 6). Compositional analyses for lubricin and cytokines were performed. Friction coefficients and local tissue shear strain measurements were coupled using new, microscale rheological analyses by lubricating neonatal bovine cartilage explants with SF alone and in a 1:1 ratio with HA (Hymovis®).

Results: Friction coefficients were not significantly different between the inflammatory and non-inflammatory pathologies (p = 0.09), and were poorly correlated with peak tissue strains at the cartilage articular surface (R² = 0.34). A subset of inflammatory SF samples induced higher tissue strains, and HA supplementation was most effective at lowering friction and tissue strains in this inflammatory subset. Across all pathologies there were clear relationships between polymorphonuclear neutrophil (PMN), IL-8, and lubricin concentrations with cartilage tissue strains.

Conclusion: These results suggest that pathological SF is characterized by distinct tribological endotypes where SF lubricating behaviors are differentially modified by viscosupplementation and are identifiable by biomarkers.

Keywords: Arthritis; Friction; Hyaluronic acid; Inflammation; Lubricin; Osteoarthritis.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Video-Audio Media

MeSH terms

Aged
Animals
Arthritis / drug therapy
Arthritis / metabolism
Biomarkers / metabolism
Cartilage, Articular*
Cattle
Cytokines / metabolism*
Female
Friction*
Glycoproteins / metabolism*
Humans
Hyaluronic Acid / therapeutic use
In Vitro Techniques
Injections, Intra-Articular
Interleukin-8 / metabolism
Male
Middle Aged
Neutrophils
Osteoarthritis, Knee / drug therapy*
Osteoarthritis, Knee / metabolism*
Patient Selection
Rheology
Stress, Mechanical
Synovial Fluid / cytology
Synovial Fluid / metabolism*
Treatment Outcome
Viscosupplementation
Viscosupplements / therapeutic use

Substances

Biomarkers
CXCL8 protein, human
Cytokines
Glycoproteins
Interleukin-8
Viscosupplements
lubricin
Hyaluronic Acid

Grants and funding

R01 AR071394/AR/NIAMS NIH HHS/United States