The infrapatellar fat pad in inflammaging, knee joint health, and osteoarthritis

The infrapatellar fat pad in inflammaging, knee joint health, and osteoarthritis
  • Steinmetz, J. D. et al. Global, regional, and national burden of osteoarthritis, 1990-2020 and projections to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet Rheumatol. 5, 508–522 (2023).

    Article 

    Google Scholar 

  • Hochberg, M. C., Cisternas, M. G. & Watkins-Castillo, S. I. United States Bone and Joint Initiative: The Burden of Musculoskeletal Diseases in the United States (BMUS). Bone Jt. Initiative USA 4, 11–12 (2020).

    Google Scholar 

  • Katz, J. N., Arant, K. R. & Loeser, R. F. Diagnosis and Treatment of Hip and Knee Osteoarthritis: A Review. JAMA 325, 568–578 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • O’Neill, T. W. & Felson, D. T. Mechanisms of Osteoarthritis (OA) Pain. Curr. Osteoporos. Rep. 16, 611–616 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Gullo, T. R. et al. Defining multiple joint osteoarthritis, its frequency and impact in a community-based cohort. Semin Arthritis Rheum. 48, 950–957 (2019).

    Article 
    PubMed 

    Google Scholar 

  • Jin, Z. et al. Incidence trend of five common musculoskeletal disorders from 1990 to 2017 at the global, regional and national level: results from the global burden of disease study 2017. Ann. Rheum. Dis. 79, 1014–1022 (2020).

    Article 
    PubMed 

    Google Scholar 

  • Furman, D. et al. Chronic inflammation in the etiology of disease across the life span. Nat. Med. 25, 1822–1832 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Losina, E. et al. Lifetime risk and age at diagnosis of symptomatic knee osteoarthritis in the US. Arthritis Care Res. 65, 703–711 (2013).

    Article 

    Google Scholar 

  • Blasioli, D. J. & Kaplan, D. L. The roles of catabolic factors in the development of osteoarthritis. Tissue Eng. Part B Rev. 20, 355–363 (2014).

    CAS 

    Google Scholar 

  • Strandberg, T. E. & Tilvis, R. S. C-reactive protein, cardiovascular risk factors, and mortality in a prospective study in the elderly. Arterioscler Thromb. Vasc. Biol. 20, 1057–1060 (2000).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Franceschi, C. et al. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann. N. Y Acad. Sci. 908, 244–254 (2000).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Metcalfe, A. et al. Abnormal loading of the major joints in knee osteoarthritis and the response to knee replacement. Gait Posture 37, 32–36 (2013).

    Article 
    PubMed 

    Google Scholar 

  • Ioan-Facsinay, A. & Kloppenburg, M. An emerging player in knee osteoarthritis: The infrapatellar fat pad. Arthritis Res. Ther. 15, 225 (2013).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Favero, M. et al. Infrapatellar fat pad features in osteoarthritis: A histopathological and molecular study. Rheumatology 56, 1784–1793 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Griffin, T. M. & Huffman, K. M. Editorial: Insulin Resistance: Releasing the Brakes on Synovial Inflammation and Osteoarthritis? Arthritis Rheumatol. 68, 1330–1333 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Sakers, A., De Siqueira, M. K., Seale, P. & Villanueva, C. J. Adipose-tissue plasticity in health and disease. Cell 185, 419–446 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Loeser, R. F., Goldring, S. R., Scanzello, C. R. & Goldring, M. B. Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum. 64, 1697–1707 (2012).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Aikawa, J. et al. Expression of calcitonin gene-related peptide in the infrapatellar fat pad in knee osteoarthritis patients. J. Orthop. Surg. Res. 12, 65 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Fontanella, C. G. et al. Investigation of biomechanical response of Hoffa’s fat pad and comparative characterization. J. Mech. Behav. Biomed. Mater. 67, 1–9 (2017).

    Article 
    PubMed 

    Google Scholar 

  • Cai, J., Xu, J. & Wang, K. Association between infrapatellar fat pad volume and knee structural changes in patients with knee osteoarthritis. J. Rheumatol. 42, 1878–1884 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Iwata, M. et al. Initial responses of articular tissues in a murine high-fat diet-induced osteoarthritis model: pivotal role of the IPFP as a cytokine fountain. PLoS One 12, 8 (2013).

    Google Scholar 

  • Barboza, E. et al. Profibrotic Infrapatellar Fat Pad Remodeling Without M1 Macrophage Polarization Precedes Knee Osteoarthritis in Mice With Diet-Induced Obesity. Arthritis Rheumatol. 69, 1221–1232 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Stocco, E. et al. Age-Dependent Remodeling in Infrapatellar Fat Pad Adipocytes and Extracellular Matrix: A Comparative Study. Front. Med. 8, 661403 (2021).

    Article 

    Google Scholar 

  • Fu, Y., Huebner, J. L., Kraus, V. B. & Griffin, T. M. Effect of Aging on Adipose Tissue Inflammation in the Knee Joints of F344BN Rats. J. Gerontol. Ser. A, Biol. Sci. Med. Sci. 71, 1131–1140 (2016).

    Article 
    CAS 

    Google Scholar 

  • Nishimuta, J. F., Bendernagel, M. F. & Levenston, M. E. Co-culture with infrapatellar fat pad differentially stimulates proteoglycan synthesis and accumulation in cartilage and meniscus tissues. Connect Tissue Res. 58, 447–455 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Kim, Y. M. & Joo, Y. B. Patellofemoral osteoarthritis. Knee Surg. Relat. Res. 24, 193–200 (2012).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Cowan, S. M., Hart, H. F., Warden, S. J. & Crossley, K. M. Infrapatellar fat pad volume is greater in individuals with patellofemoral joint osteoarthritis and associated with pain. Rheumatol. Int. 35, 1439–1442 (2015).

    Article 
    PubMed 

    Google Scholar 

  • Harasymowicz, N. S. et al. Regional Differences Between Perisynovial and Infrapatellar Adipose Tissue Depots and Their Response to Class II and Class III Obesity in Patients With Osteoarthritis. Arthritis Rheumatol. 69, 1396–1406 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Vaure, C. & Liu, Y. A comparative review of toll-like receptor 4 expression and functionality in different animal species. Front Immunol. 10, 316 (2014).

    Google Scholar 

  • Fujisaka, S. et al. Regulatory mechanisms for adipose tissue M1 and M2 macrophages in diet-induced obese mice. Diabetes 58, 2574–2582 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • McGillicuddy, F. C. et al. Long-term exposure to a high-fat diet results in the development of glucose intolerance and insulin resistance in interleukin-1 receptor I-deficient mice. Am. J. Physiol. Endocrinol. Metab. 305, e834–e844 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Hepler, C. & Gupta, R. K. The expanding problem of adipose depot remodeling and postnatal adipocyte progenitor recruitment. Mol. Cell Endocrinol. 445, 95–108 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Hemmeryckx, B., Hoylaerts, M. F. & Lijnen, H. R. Effect of premature aging on murine adipose tissue. Exp. Gerontol. 47, 256–262 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Wu, D. et al. Aging up-regulates expression of inflammatory mediators in mouse adipose tissue. J. Immunol. 179, 4829–4839 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Coppé, J. P. et al. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol. 6, 2853–2868 (2008).

    Article 
    PubMed 

    Google Scholar 

  • Price, J. S. et al. The role of chondrocyte senescence in osteoarthritis. Aging Cell 1, 57–65 (2002).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Sayed, N. et al. An inflammatory aging clock (iAge) based on deep learning tracks multimorbidity, immunosenescence, frailty and cardiovascular aging. Nat. aging 1, 598–615 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bonfante, H. L. et al. CCL2, CXCL8, CXCL9 and CXCL10 serum levels increase with age but are not altered by treatment with hydroxychloroquine in patients with osteoarthritis of the knees. Int. J. Rheum. Dis. 20, 1958–1964 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Schafer, M. J. et al. The senescence-associated secretome as an indicator of age and medical risk. JCI Insight 5, e133668 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Sohn, D. H. et al. Plasma proteins present in osteoarthritic synovial fluid can stimulate cytokine production via Toll-like receptor 4. Arthritis Res Ther. 14, R7 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Scanzello, C. R., Plaas, A. & Crow, M. K. Innate immune system activation in osteoarthritis: is osteoarthritis a chronic wound? Curr. Opin. Rheumatol. 20, 565–572 (2008).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Borzì, R. M. et al. Human chondrocytes express functional chemokine receptors and release matrix-degrading enzymes in response to C-X-C and C-C chemokines. Arthritis Rheum. 43, 1734–1741 (2000).

    Article 
    PubMed 

    Google Scholar 

  • Mazzetti, I. et al. A role for chemokines in the induction of chondrocyte phenotype modulation. Arthritis Rheum. 50, 12–22 (2004).

    Article 

    Google Scholar 

  • Chuckpaiwong, B., Charles, H. C., Kraus, V. B., Guilak, F. & Nunley, J. A. Age-associated increases in the size of the infrapatellar fat pad in knee osteoarthritis as measured by 3T MRI. J. Orthop. Res. 28, 1149–1154 (2010).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Klein-Wieringa, I. R. et al. Inflammatory Cells in Patients with Endstage Knee Osteoarthritis: A Comparison between the Synovium and the Infrapatellar Fat Pad. J. Rheumatol. 43, 771–778 (2016).

    Article 
    PubMed 

    Google Scholar 

  • Cascio, G., Schiera, G. & Di Liegro, I. Dietary fatty acids in metabolic syndrome, diabetes and cardiovascular diseases. Curr. Diab. Rev. 8, 2–17 (2012).

    Article 
    CAS 

    Google Scholar 

  • Serhan, C. N. The resolution of inflammation: the devil in the flask and in the details. FASEB J. 25, 1441–1448 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Gierman, L. M. et al. Metabolic profiling reveals differences in concentrations of oxylipins and fatty acids secreted by the infrapatellar fat pad of end-stage osteoarthritis and normal donors. Arthritis Rheum. 65, 2606–2614 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Mustonen, A. M. et al. Distinct fatty acid signatures in infrapatellar fat pad and synovial fluid of patients with osteoarthritis versus rheumatoid arthritis. Arthritis Res Ther. 21, 124 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Conde, J. et al. Expanding the adipokine network in cartilage: identification and regulation of novel factors in human and murine chondrocytes. Ann. Rheum. Dis. 70, 551–559 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Conde, J. et al. Identification of novel adipokines in the joint. Differential expression in healthy and osteoarthritis tissues. PLoS One 10, e0123601 (2015).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Conde, J. et al. Differential expression of adipokines in infrapatellar fat pad (IPFP) and synovium of osteoarthritis patients and healthy individuals. Ann. Rheum. Dis. 73, 631–633 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Zhang, C. et al. FABP4 as a biomarker for knee osteoarthritis. Biomark. Med. 12, 107–118 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Belluzzi, E. et al. Infrapatellar fat pad gene expression and protein production in patients with and without osteoarthritis. Int. J. Mol. Sci. 21, 6016 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Dumond, H. et al. Evidence for a key role of leptin in osteoarthritis. Arthritis Rheum. 48, 3118–3129 (2003).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Presle, N. et al. Differential distribution of adipokines between serum and synovial fluid in patients with osteoarthritis. Contribution of joint tissues to their articular production. Osteoarthr. Cartil. 14, 690–695 (2006).

    Article 
    CAS 

    Google Scholar 

  • Bao, J. P. et al. Leptin plays a catabolic role on articular cartilage. Mol. Biol. Rep. 37, 3265–3272 (2010).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Vuolteenaho, K. et al. Leptin Enhances Synthesis of Proinflammatory Mediators in Human Osteoarthritic Cartilage— Mediator Role of NO in Leptin-Induced, IL-6, and IL-8 Production. Mediators Inflamm. 1, 345838 (2009).

    Google Scholar 

  • Griffin, T. M., Huebner, J. L., Kraus, V. B. & Guilak, F. Extreme obesity due to impaired leptin signaling in mice does not cause knee osteoarthritis. Arthritis Rheumatism 60, 2935–2944 (2009).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Otero, M. et al. Changes in plasma levels of fat-derived hormones adiponectin, leptin, resistin and visfatin in patients with rheumatoid arthritis. Ann. Rheum. Dis. 65, 1198–1201 (2006).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Calvet, J. et al. Synovial fluid adipokines are associated with clinical severity in knee osteoarthritis: a cross-sectional study in female patients with joint effusion. Arthritis Res Ther. 18, 207 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bohnsack, M. et al. Influence of an infrapatellar fat pad edema on patellofemoral biomechanics and knee kinematics: a possible relation to the anterior knee pain syndrome. Arch. Orthop. Trauma Surg. 129, 1025–1030 (2009).

    Article 
    PubMed 

    Google Scholar 

  • Son, Y. M. et al. Immunomodulatory effect of resistin in human dendritic cells stimulated with lipoteichoic acid from Staphylococcus aureus. Biochem Biophys. Res. Commun. 376, 599–604 (2008).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Shibata, R. et al. Adiponectin stimulates angiogenesis in response to tissue ischemia through stimulation of amp-activated protein kinase signaling. J. Biol. Chem. 279, 28670–28674 (2004).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Kondo, M. et al. Caloric restriction stimulates revascularization in response to ischemia via adiponectin-mediated activation of endothelial nitric-oxide synthase. J. Biol. Chem. 284, 1718–1724 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wang, K. et al. Serum levels of interleukin-17 and adiponectin are associated with infrapatellar fat pad volume and signal intensity alteration in patients with knee osteoarthritis. Arthritis Res. Ther. 18, 1–7 (2016).

    Article 

    Google Scholar 

  • Murrell, G. A., Jang, D. & Williams, R. J. Nitric oxide activates metalloprotease enzymes in articular cartilage. Biochem. Biophys. Res. Commun. 206, 15–21 (1995).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Kang, E. H. et al. Adiponectin is a potential catabolic mediator in osteoarthritis cartilage. Arthritis Res. Ther. 12, R231 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Miyachi, Y. et al. A reduced M1- like/M2-like ratio of macrophages in healthy adipose tissue expansion during SGLT2 inhibition. Sci. Rep. 8, 16113 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bastiaansen-Jenniskens, Y. M. et al. Infrapatellar fat pad of patients with end-stage osteoarthritis inhibits catabolic mediators in cartilage. Ann. Rheum. Dis. 71, 288–294 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • de Jong, A. J. et al. Lack of high BMI-related features in adipocytes and inflammatory cells in the infrapatellar fat pad (IFP). Arthritis Res. Ther. 19, 186 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Clockaerts, S. et al. Cytokine production by infrapatellar fat pad can be stimulated by interleukin 1β and inhibited by peroxisome proliferator activated receptor α agonist. Ann. Rheum. Dis. 71, 1012–1018 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Belluzzi, E. et al. Contribution of Infrapatellar Fat Pad and Synovial Membrane to Knee Osteoarthritis Pain. Biomed. Res. Int. 1, 6390182 (2019).

    Google Scholar 

  • Distel, E. et al. The infrapatellar fat pad in knee osteoarthritis: an important source of interleukin-6 and its soluble receptor. Arthritis Rheum. 60, 3374–3377 (2009).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • He, J. et al. Infrapatellar fat pad aggravates degeneration of acute traumatized cartilage: a possible role for interleukin-6. Osteoarthr. Cartil. 25, 138–145 (2017).

    Article 
    CAS 

    Google Scholar 

  • Schnoor, M., Alcaide, P., Voisin, M. B. & van Buul, J. D. Recruitment of Immune Cells into Inflamed Tissues: Consequences for Endothelial Barrier Integrity and Tissue Functionality. Mediators Inflamm. 1, 1561368 (2016).

    Google Scholar 

  • Takano, S. et al. Vascular Endothelial Growth Factor Is Regulated by the Canonical and Noncanonical Transforming Growth Factor-β Pathway in Synovial Fibroblasts Derived from Osteoarthritis Patients. BioMed. Res. Int. 6959056, 1–6 (2019).

    Article 

    Google Scholar 

  • Haywood, L. et al. Inflammation and angiogenesis in osteoarthritis. Arthritis Rheum. 48, 2173–2177 (2003).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Bennell, K., Hodges, P., Mellor, R., Bexander, C. & Souvlis, T. The nature of anterior knee pain following injection of hypertonic saline into the infrapatellar fat pad. J. Orthop. Res. 22, 116–121 (2004).

    Article 
    PubMed 

    Google Scholar 

  • Ballegaard, C. et al. Knee pain and inflammation in the infrapatellar fat pad estimated by conventional and dynamic contrast-enhanced magnetic resonance imaging in obese patients with osteoarthritis: a cross-sectional study. Osteoarthr. Cartil. 22, 933–940 (2014).

    Article 
    CAS 

    Google Scholar 

  • Han, W. et al. Hypointense signals in the infrapatellar fat pad assessed by magnetic resonance imaging are associated with knee symptoms and structure in older adults: a cohort study. Arthritis Res Ther. 18, 234 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bas, S. et al. Adipokines correlate with pain in lower limb osteoarthritis: different associations in hip and knee. Int Orthop. 38, 2577–2583 (2014).

    Article 
    PubMed 

    Google Scholar 

  • Inomata, K. et al. Time course analyses of structural changes in the infrapatellar fat pad and synovial membrane during inflammation-induced persistent pain development in rat knee joint. BMC Musculoskelet. Disord. 20, 1–10 (2019).

    Article 

    Google Scholar 

  • An, J. et al. Inhibition of fibrotic changes in infrapatellar fat pad alleviates persistent pain and articular cartilage degeneration in monoiodoacetic acid-induced rat arthritis model. Osteoarthr. Cartil. 29, 380–388 (2020).

    Article 

    Google Scholar 

  • Bohnsack, M., Meier, F. & Walter, G. F. Distribution of substance-P nerves inside the infrapatellar fat pad and the adjacent synovial tissue: a neurohistological approach to anterior knee pain syndrome. Arch. Orthop. Trauma Surg. 125, 592–597 (2005).

    Article 
    PubMed 

    Google Scholar 

  • Stanisz, A. M. Neurogenic inflammation: role of substance P. NeuroImmune Biol. 1, 373–378 (2001).

    Article 
    CAS 

    Google Scholar 

  • Hoffa, A. The Influence of the Adipose Tissue with Regard to the Pathology of the Knee Joint. JAMA 43, 795–796 (1904).

    Article 

    Google Scholar 

  • Kimura, T. et al. C-type natriuretic peptide ameliorates pulmonary fibrosis by acting on lung fibroblasts in mice. Respir. Res. 17, 19 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Davis, J. E. et al. Effusion-synovitis and infrapatellar fat pad signal intensity alteration differentiate accelerated knee osteoarthritis. Rheumatology 58, 418–426 (2019).

    Article 
    PubMed 

    Google Scholar 

  • Teichtahl, A. J. et al. A large infrapatellar fat pad protects against knee pain and lateral tibial cartilage volume loss. Arthritis Res Ther. 10, 318 (2015).

    Article 

    Google Scholar 

  • Zuk, P. A. et al. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 7, 211–228 (2001).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Manferdini, C. et al. Adipose-derived mesenchymal stem cells exert antiinflammatory effects on chondrocytes and synoviocytes from osteoarthritis patients through prostaglandin E2. Arthritis Rheum. 65, 1271–1281 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Desando, G. et al. Intra-articular delivery of adipose derived stromal cells attenuates osteoarthritis progression in an experimental rabbit model. Arthritis Res Ther. 15, R22 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Pers, Y. M. et al. Adipose Mesenchymal Stromal Cell-Based Therapy for Severe Osteoarthritis of the Knee: A Phase I Dose-Escalation Trial. Stem Cells Transl. Med 5, 847–856 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Garcia, J. et al. Chondrogenic Potency Analyses of Donor-Matched Chondrocytes and Mesenchymal Stem Cells Derived from Bone Marrow, Infrapatellar Fat Pad, and Subcutaneous Fat. Stem Cells Int 1, 6969726 (2016).

    Google Scholar 

  • Mantripragada, V. et al. Donor-matched comparison of chondrogenic progenitors resident in human infrapatellar fat pad, synovium, and periosteum-implications for cartilage repair. Connect Tissue Res. 60, 597–610 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Luo, L., Thorpe, S. D., Buckley, C. T. & Kelly, D. J. The effects of dynamic compression on the development of cartilage grafts engineered using bone marrow and infrapatellar fat pad derived stem cells. Biomed. Mater. 10, 055011 (2015).

    Article 
    PubMed 

    Google Scholar 

  • Prabhakar, A., Lynch, A. P. & Ahearne, M. Self-Assembled Infrapatellar Fat-Pad Progenitor Cells on a Poly-ε-Caprolactone Film For Cartilage Regeneration. Artif. Organs 40, 376–384 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Kouroupis, D., Kaplan, L. D. & Best, T. M. Human infrapatellar fat pad mesenchymal stem cells show immunomodulatory exosomal signatures. Sci. Rep. 12, 3609 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Skalska, U. et al. Articular and subcutaneous adipose tissues of rheumatoid arthritis patients represent equal sources of immunoregulatory mesenchymal stem cells. Autoimmunity 50, 441–450 (2017).

    Article 
    PubMed 

    Google Scholar 

  • Meurot, C. et al. Targeting the GLP-1/GLP-1R axis to treat osteoarthritis: A new opportunity? J. Orthop. Transl. 32, 121–129 (2022).

    CAS 

    Google Scholar 

  • Daheshia, M. & Yao, J. Q. The interleukin 1beta pathway in the pathogenesis of osteoarthritis. J. Rheumatol. 35, 2306–2312 (2008).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Akeson, G. & Malemud, C. J. A Role for Soluble IL-6 Receptor in Osteoarthritis. J. Funct. Morphol. Kinesiol. 2, 27 (2017).

    Article 
    PubMed 

    Google Scholar 

  • García-Manrique, M. et al. Synovial fluid but not plasma interleukin-8 is associated with clinical severity and inflammatory markers in knee osteoarthritis women with joint effusion. Sci. Rep. 11, 5258 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Nagao, M. et al. Vascular Endothelial Growth Factor in Cartilage Development and Osteoarthritis. Sci. Rep. 7, 13027 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Yan, M., Zhang, J., Yang, H. & Sun, Y. The role of leptin in osteoarthritis. Medicine 97, e0257 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Zhao, C. W. et al. An Update on the Emerging Role of Resistin on the Pathogenesis of Osteoarthritis. Mediators Inflamm. 1, 1532164 (2019).

    Google Scholar 

  • Feng, X., Xiao, J. & Bai, L. Role of adiponectin in osteoarthritis. Front. cell developmental Biol. 10, 992764 (2022).

    Article 

    Google Scholar 

  • link