Infrapatellar fat pad of patients with end-stage osteoarthritis inhibits catabolic mediators in cartilage

Objective Adipose tissue is known to release inflammatory cytokines and growth factors. In this exploratory study, the authors examined whether the infrapatellar fat pad (IPFP) closely located to cartilage in the knee joint can affect cartilage metabolism. In addition, the authors analysed whether the macrophage types present in IPFP could explain the effect on cartilage. Methods IPFP explants obtained during total knee replacement of 29 patients with osteoarthritis (OA) were used to make fat-conditioned medium (FCM). Explants of bovine cartilage were cultured with or without FCM. Nitric oxide (NO) and glycosaminoglycan release and gene expression of matrix-degrading enzymes in cartilage were analysed. To stimulate catabolic processes in the cartilage, the authors added interleukin 1β, and the effect of six FCMs was evaluated. The presence of different types of macrophages (CD68+, CD86+ and CD206+) in OA IPFPs was compared with subcutaneous adipose tissue samples and IPFP samples from patients with an anterior cruciate ligament rupture. Results FCM alone reduced NO and glycosaminoglycan release and matrix metalloproteinase (MMP)1 gene expression by the cartilage. Moreover, when catabolic conditions were enhanced with interleukin 1β, FCM inhibited NO production as well as MMP1 and MMP3 gene expression and increased collagen type II gene expression. Significantly more CD206+ cells were present in OA IPFP samples than in subcutaneous fat or anterior cruciate ligament IPFP samples. Conclusion In contrast to the authors' expectations, medium conditioned by end-stage OA IPFP inhibited catabolic processes in cartilage. CD206+ cells present in the IPFPs used for making the FCM might have contributed to the inhibition of catabolic processes in the cartilage.

[1]  R. Toes,et al.  The infrapatellar fat pad of patients with osteoarthritis has an inflammatory phenotype , 2011, Annals of the rheumatic diseases.

[2]  A. Fosang,et al.  Identifying the human aggrecanase. , 2010, Osteoarthritis and cartilage.

[3]  D. Young,et al.  Lipophilic statins prevent matrix metalloproteinase-mediated cartilage collagen breakdown by inhibiting protein geranylgeranylation , 2010, Annals of the rheumatic diseases.

[4]  Li-Dong Wu,et al.  Increased serum concentrations of visfatin and its production by different joint tissues in patients with osteoarthritis , 2010, Clinical chemistry and laboratory medicine.

[5]  Luke Barron,et al.  Macrophages: Master Regulators of Inflammation and Fibrosis , 2010, Seminars in liver disease.

[6]  J. Verhaar,et al.  The infrapatellar fat pad should be considered as an active osteoarthritic joint tissue: a narrative review. , 2010, Osteoarthritis and cartilage.

[7]  J. Verhaar,et al.  Elevated Levels of Cartilage Oligomeric Matrix Protein during In Vitro Cartilage Matrix Generation Decrease Collagen Fibril Diameter , 2010, Cartilage.

[8]  Emily K Anderson,et al.  Adipose tissue recruitment of leukocytes , 2010, Current opinion in lipidology.

[9]  G. Steinberg,et al.  Adipose tissue as an endocrine organ , 2010, Molecular and Cellular Endocrinology.

[10]  H. Tsutsui,et al.  Natural Killer T Cells Are Involved in Adipose Tissues Inflammation and Glucose Intolerance in Diet-Induced Obese Mice , 2010, Arteriosclerosis, thrombosis, and vascular biology.

[11]  K. Clément,et al.  Human adipose tissue macrophages: m1 and m2 cell surface markers in subcutaneous and omental depots and after weight loss. , 2009, The Journal of clinical endocrinology and metabolism.

[12]  E. Distel,et al.  The infrapatellar fat pad in knee osteoarthritis: an important source of interleukin-6 and its soluble receptor. , 2009, Arthritis and rheumatism.

[13]  T. Kadowaki,et al.  CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity , 2009, Nature Medicine.

[14]  Carey N. Lumeng,et al.  T-ing up inflammation in fat , 2009, Nature Medicine.

[15]  K. Clément,et al.  Deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice , 2009, Nature Medicine.

[16]  S. Middeldorp,et al.  Association between weight or body mass index and hand osteoarthritis: a systematic review , 2009, Annals of the rheumatic diseases.

[17]  J. Verhaar,et al.  Proteoglycan production is required in initial stages of new cartilage matrix formation but inhibits integrative cartilage repair , 2009, Journal of tissue engineering and regenerative medicine.

[18]  A. Saltiel,et al.  Phenotypic Switching of Adipose Tissue Macrophages With Obesity Is Generated by Spatiotemporal Differences in Macrophage Subtypes , 2008, Diabetes.

[19]  J. Edwards,et al.  Exploring the full spectrum of macrophage activation , 2008, Nature Reviews Immunology.

[20]  T. Stulnig,et al.  Adipose tissue macrophages. , 2007, Immunology letters.

[21]  G. Zlabinger,et al.  Human adipose tissue macrophages are of an anti-inflammatory phenotype but capable of excessive pro-inflammatory mediator production , 2007, International Journal of Obesity.

[22]  A. Saltiel,et al.  Obesity induces a phenotypic switch in adipose tissue macrophage polarization. , 2007, The Journal of clinical investigation.

[23]  Alberto Mantovani,et al.  Transcriptional Profiling of the Human Monocyte-to-Macrophage Differentiation and Polarization: New Molecules and Patterns of Gene Expression1 , 2006, The Journal of Immunology.

[24]  Harrie Weinans,et al.  Biochemical and functional modulation of the cartilage collagen network by IGF1, TGFβ2 and FGF2 , 2006 .

[25]  A. Madan,et al.  Most of the interleukin 1 receptor antagonist, cathepsin S, macrophage migration inhibitory factor, nerve growth factor, and interleukin 18 release by explants of human adipose tissue is by the non-fat cells, not by the adipocytes. , 2006, Metabolism: clinical and experimental.

[26]  S. Bierma-Zeinstra,et al.  Body mass index associated with onset and progression of osteoarthritis of the knee but not of the hip: The Rotterdam Study , 2006, Annals of the rheumatic diseases.

[27]  F. Lapicque,et al.  Differential distribution of adipokines between serum and synovial fluid in patients with osteoarthritis. Contribution of joint tissues to their articular production. , 2006, Osteoarthritis and cartilage.

[28]  T. Ottenhoff,et al.  Phenotypic and functional profiling of human proinflammatory type‐1 and anti‐inflammatory type‐2 macrophages in response to microbial antigens and IFN‐γ‐ and CD40L‐mediated costimulation , 2006, Journal of leukocyte biology.

[29]  G. Fantuzzi.  Adipose tissue, adipokines, and inflammation. , 2005, The Journal of allergy and clinical immunology.

[30]  B. Bresnihan,et al.  Synovial tissue inflammation in early and late osteoarthritis , 2005, Annals of the rheumatic diseases.

[31]  J. Flier,et al.  Adipose Tissue as an Endocrine Organ , 2014 .

[32]  A. Madan,et al.  Comparison of the release of adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and subcutaneous abdominal adipose tissues of obese humans. , 2004, Endocrinology.

[33]  K N Frayn,et al.  Integrative physiology of human adipose tissue , 2003, International Journal of Obesity.

[34]  A. Rowan,et al.  Transforming growth factor beta 1 and insulin-like growth factor 1 block collagen degradation induced by oncostatin M in combination with tumour necrosis factor alpha from bovine cartilage. , 2003, Annals of the rheumatic diseases.

[35]  Y. Matsusue,et al.  Cytokine production in the infrapatellar fat pad: another source of cytokines in knee synovial fluids , 2003, Annals of the rheumatic diseases.

[36]  E. Pearce,et al.  Differential Regulation of Nitric Oxide Synthase-2 and Arginase-1 by Type 1/Type 2 Cytokines In Vivo: Granulomatous Pathology Is Shaped by the Pattern of l-Arginine Metabolism1 , 2001, The Journal of Immunology.

[37]  S. Abramson,et al.  Osteoarthritis, an inflammatory disease: potential implication for the selection of new therapeutic targets. , 2001, Arthritis and rheumatism.

[38]  S Gordon,et al.  Interleukin 4 potently enhances murine macrophage mannose receptor activity: a marker of alternative immunologic macrophage activation , 1992, The Journal of experimental medicine.

[39]  S. Tannenbaum,et al.  Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. , 1982, Analytical biochemistry.

[40]  John N Fain,et al.  Release of interleukins and other inflammatory cytokines by human adipose tissue is enhanced in obesity and primarily due to the nonfat cells. , 2006, Vitamins and hormones.

[41]  S. Gordon.  Alternative activation of macrophages , 2003, Nature Reviews Immunology.