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


Journal

npj aging
ISSN: 2731-6068
Titre abrégé: NPJ Aging
Pays: England
ID NLM: 9918402285106676

Informations de publication

Date de publication:
15 Jul 2024
Historique:
received: 23 03 2024
accepted: 12 06 2024
medline: 16 7 2024
pubmed: 16 7 2024
entrez: 15 7 2024
Statut: epublish

Résumé

Osteoarthritis (OA) is the most common form of arthritis and accounts for nearly $140 billion in annual healthcare expenditures only in the United States. Obesity, aging, and joint injury are major risk factors for OA development and progression, but the mechanisms contributing to pathology remain unclear. Emerging evidence suggests that cellular dysregulation and inflammation in joint tissues, including intra-articular adipose tissue depots, may contribute to disease severity. In particular, the infrapatellar fat pad (IFP), located in the knee joint, which provides a protective cushion for joint loading, also secretes multiple endocrine factors and inflammatory cytokines (inflammaging) that can regulate joint physiology and disease. Correlates of cartilage degeneration and OA-associated disease severity include inflammation and fibrosis of IFP in model organisms and human studies. In this article, we discuss recent progress in understanding the roles and regulation of intra-articular fat tissue in regulating joint biology and OA.

Identifiants

pubmed: 39009582
doi: 10.1038/s41514-024-00159-z
pii: 10.1038/s41514-024-00159-z
doi:

Types de publication

Journal Article Review

Langues

eng

Pagination

34

Subventions

Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)
ID : DK123356

Informations de copyright

© 2024. The Author(s).

Références

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).
doi: 10.1016/S2665-9913(23)00163-7
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).
Katz, J. N., Arant, K. R. & Loeser, R. F. Diagnosis and Treatment of Hip and Knee Osteoarthritis: A Review. JAMA 325, 568–578 (2021).
pubmed: 33560326 pmcid: 8225295 doi: 10.1001/jama.2020.22171
O’Neill, T. W. & Felson, D. T. Mechanisms of Osteoarthritis (OA) Pain. Curr. Osteoporos. Rep. 16, 611–616 (2018).
pubmed: 30155845 pmcid: 6153568 doi: 10.1007/s11914-018-0477-1
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).
pubmed: 30390991 doi: 10.1016/j.semarthrit.2018.10.001
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).
pubmed: 32414807 doi: 10.1136/annrheumdis-2020-217050
Furman, D. et al. Chronic inflammation in the etiology of disease across the life span. Nat. Med. 25, 1822–1832 (2019).
pubmed: 31806905 pmcid: 7147972 doi: 10.1038/s41591-019-0675-0
Losina, E. et al. Lifetime risk and age at diagnosis of symptomatic knee osteoarthritis in the US. Arthritis Care Res. 65, 703–711 (2013).
doi: 10.1002/acr.21898
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).
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).
pubmed: 10764673 doi: 10.1161/01.ATV.20.4.1057
Franceschi, C. et al. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann. N. Y Acad. Sci. 908, 244–254 (2000).
pubmed: 10911963 doi: 10.1111/j.1749-6632.2000.tb06651.x
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).
pubmed: 22841587 doi: 10.1016/j.gaitpost.2012.04.018
Ioan-Facsinay, A. & Kloppenburg, M. An emerging player in knee osteoarthritis: The infrapatellar fat pad. Arthritis Res. Ther. 15, 225 (2013).
pubmed: 24367915 pmcid: 3979009 doi: 10.1186/ar4422
Favero, M. et al. Infrapatellar fat pad features in osteoarthritis: A histopathological and molecular study. Rheumatology 56, 1784–1793 (2017).
pubmed: 28957567 doi: 10.1093/rheumatology/kex287
Griffin, T. M. & Huffman, K. M. Editorial: Insulin Resistance: Releasing the Brakes on Synovial Inflammation and Osteoarthritis? Arthritis Rheumatol. 68, 1330–1333 (2016).
pubmed: 26749517 pmcid: 5371020 doi: 10.1002/art.39586
Sakers, A., De Siqueira, M. K., Seale, P. & Villanueva, C. J. Adipose-tissue plasticity in health and disease. Cell 185, 419–446 (2022).
pubmed: 35120662 pmcid: 11152570 doi: 10.1016/j.cell.2021.12.016
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).
pubmed: 22392533 pmcid: 3366018 doi: 10.1002/art.34453
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).
pubmed: 28431586 pmcid: 5399802 doi: 10.1186/s13018-017-0568-1
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).
pubmed: 27936429 doi: 10.1016/j.jmbbm.2016.11.024
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).
pubmed: 26276969 doi: 10.3899/jrheum.150175
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).
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).
pubmed: 28141918 pmcid: 5449220 doi: 10.1002/art.40056
Stocco, E. et al. Age-Dependent Remodeling in Infrapatellar Fat Pad Adipocytes and Extracellular Matrix: A Comparative Study. Front. Med. 8, 661403 (2021).
doi: 10.3389/fmed.2021.661403
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).
doi: 10.1093/gerona/glv151
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).
pubmed: 27726455 doi: 10.1080/03008207.2016.1245728
Kim, Y. M. & Joo, Y. B. Patellofemoral osteoarthritis. Knee Surg. Relat. Res. 24, 193–200 (2012).
pubmed: 23269956 pmcid: 3526755 doi: 10.5792/ksrr.2012.24.4.193
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).
pubmed: 25782586 doi: 10.1007/s00296-015-3250-0
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).
pubmed: 28320058 doi: 10.1002/art.40102
Vaure, C. & Liu, Y. A comparative review of toll-like receptor 4 expression and functionality in different animal species. Front Immunol. 10, 316 (2014).
Fujisaka, S. et al. Regulatory mechanisms for adipose tissue M1 and M2 macrophages in diet-induced obese mice. Diabetes 58, 2574–2582 (2009).
pubmed: 19690061 pmcid: 2768159 doi: 10.2337/db08-1475
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).
pubmed: 23921145 pmcid: 3798700 doi: 10.1152/ajpendo.00297.2013
Hepler, C. & Gupta, R. K. The expanding problem of adipose depot remodeling and postnatal adipocyte progenitor recruitment. Mol. Cell Endocrinol. 445, 95–108 (2017).
pubmed: 27743993 doi: 10.1016/j.mce.2016.10.011
Hemmeryckx, B., Hoylaerts, M. F. & Lijnen, H. R. Effect of premature aging on murine adipose tissue. Exp. Gerontol. 47, 256–262 (2012).
pubmed: 22265801 doi: 10.1016/j.exger.2012.01.001
Wu, D. et al. Aging up-regulates expression of inflammatory mediators in mouse adipose tissue. J. Immunol. 179, 4829–4839 (2007).
pubmed: 17878382 doi: 10.4049/jimmunol.179.7.4829
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).
pubmed: 19053174 doi: 10.1371/journal.pbio.0060301
Price, J. S. et al. The role of chondrocyte senescence in osteoarthritis. Aging Cell 1, 57–65 (2002).
pubmed: 12882354 doi: 10.1046/j.1474-9728.2002.00008.x
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).
pubmed: 34888528 pmcid: 8654267 doi: 10.1038/s43587-021-00082-y
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).
pubmed: 25955863 doi: 10.1111/1756-185X.12589
Schafer, M. J. et al. The senescence-associated secretome as an indicator of age and medical risk. JCI Insight 5, e133668 (2020).
pubmed: 32554926 pmcid: 7406245 doi: 10.1172/jci.insight.133668
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).
pubmed: 22225630 pmcid: 3392793 doi: 10.1186/ar3555
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).
pubmed: 18698179 doi: 10.1097/BOR.0b013e32830aba34
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).
pubmed: 10943863 doi: 10.1002/1529-0131(200008)43:8<1734::AID-ANR9>3.0.CO;2-B
Mazzetti, I. et al. A role for chemokines in the induction of chondrocyte phenotype modulation. Arthritis Rheum. 50, 12–22 (2004).
doi: 10.1002/art.11474
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).
pubmed: 20225314 pmcid: 3625521 doi: 10.1002/jor.21125
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).
pubmed: 26980579 doi: 10.3899/jrheum.151068
Cascio, G., Schiera, G. & Di Liegro, I. Dietary fatty acids in metabolic syndrome, diabetes and cardiovascular diseases. Curr. Diab. Rev. 8, 2–17 (2012).
doi: 10.2174/157339912798829241
Serhan, C. N. The resolution of inflammation: the devil in the flask and in the details. FASEB J. 25, 1441–1448 (2011).
pubmed: 21532053 pmcid: 3228345 doi: 10.1096/fj.11-0502ufm
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).
pubmed: 23839996 doi: 10.1002/art.38081
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).
pubmed: 31118103 pmcid: 6532171 doi: 10.1186/s13075-019-1914-y
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).
pubmed: 21216818 doi: 10.1136/ard.2010.132399
Conde, J. et al. Identification of novel adipokines in the joint. Differential expression in healthy and osteoarthritis tissues. PLoS One 10, e0123601 (2015).
pubmed: 25853553 pmcid: 4390373 doi: 10.1371/journal.pone.0123601
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).
pubmed: 24099837 doi: 10.1136/annrheumdis-2013-204189
Zhang, C. et al. FABP4 as a biomarker for knee osteoarthritis. Biomark. Med. 12, 107–118 (2018).
pubmed: 29393670 doi: 10.2217/bmm-2017-0207
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).
pubmed: 32825633 pmcid: 7503946 doi: 10.3390/ijms21176016
Dumond, H. et al. Evidence for a key role of leptin in osteoarthritis. Arthritis Rheum. 48, 3118–3129 (2003).
pubmed: 14613274 doi: 10.1002/art.11303
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).
doi: 10.1016/j.joca.2006.01.009
Bao, J. P. et al. Leptin plays a catabolic role on articular cartilage. Mol. Biol. Rep. 37, 3265–3272 (2010).
pubmed: 19876764 doi: 10.1007/s11033-009-9911-x
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).
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).
pubmed: 19790050 doi: 10.1002/art.24854
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).
pubmed: 16414972 pmcid: 1798289 doi: 10.1136/ard.2005.046540
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).
pubmed: 27629533 pmcid: 5024464 doi: 10.1186/s13075-016-1103-1
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).
pubmed: 17053945 doi: 10.1007/s00402-006-0237-z
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).
pubmed: 18805395 doi: 10.1016/j.bbrc.2008.09.037
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).
pubmed: 15123726 doi: 10.1074/jbc.M402558200
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).
pubmed: 18990685 pmcid: 2615500 doi: 10.1074/jbc.M805301200
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).
doi: 10.1186/s13075-016-1088-9
Murrell, G. A., Jang, D. & Williams, R. J. Nitric oxide activates metalloprotease enzymes in articular cartilage. Biochem. Biophys. Res. Commun. 206, 15–21 (1995).
pubmed: 7529496 doi: 10.1006/bbrc.1995.1003
Kang, E. H. et al. Adiponectin is a potential catabolic mediator in osteoarthritis cartilage. Arthritis Res. Ther. 12, R231 (2010).
pubmed: 21194467 pmcid: 3046544 doi: 10.1186/ar3218
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).
pubmed: 30382157 pmcid: 6208395 doi: 10.1038/s41598-018-34305-x
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).
pubmed: 21998115 doi: 10.1136/ard.2011.153858
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).
pubmed: 28800775 pmcid: 5553811 doi: 10.1186/s13075-017-1395-9
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).
pubmed: 22307941 doi: 10.1136/annrheumdis-2011-200688
Belluzzi, E. et al. Contribution of Infrapatellar Fat Pad and Synovial Membrane to Knee Osteoarthritis Pain. Biomed. Res. Int. 1, 6390182 (2019).
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).
pubmed: 19877065 doi: 10.1002/art.24881
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).
doi: 10.1016/j.joca.2016.09.001
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).
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).
doi: 10.1155/2019/6959056
Haywood, L. et al. Inflammation and angiogenesis in osteoarthritis. Arthritis Rheum. 48, 2173–2177 (2003).
pubmed: 12905470 doi: 10.1002/art.11094
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).
pubmed: 14656669 doi: 10.1016/S0736-0266(03)00162-1
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).
doi: 10.1016/j.joca.2014.04.018
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).
pubmed: 27729069 pmcid: 5059934 doi: 10.1186/s13075-016-1130-y
Bas, S. et al. Adipokines correlate with pain in lower limb osteoarthritis: different associations in hip and knee. Int Orthop. 38, 2577–2583 (2014).
pubmed: 25005460 doi: 10.1007/s00264-014-2416-9
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).
doi: 10.1186/s12891-018-2391-1
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).
doi: 10.1016/j.joca.2020.12.014
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).
pubmed: 15891922 doi: 10.1007/s00402-005-0796-4
Stanisz, A. M. Neurogenic inflammation: role of substance P. NeuroImmune Biol. 1, 373–378 (2001).
doi: 10.1016/S1567-7443(01)80033-8
Hoffa, A. The Influence of the Adipose Tissue with Regard to the Pathology of the Knee Joint. JAMA 43, 795–796 (1904).
doi: 10.1001/jama.1904.92500120002h
Kimura, T. et al. C-type natriuretic peptide ameliorates pulmonary fibrosis by acting on lung fibroblasts in mice. Respir. Res. 17, 19 (2016).
pubmed: 26895702 pmcid: 4761143 doi: 10.1186/s12931-016-0335-6
Davis, J. E. et al. Effusion-synovitis and infrapatellar fat pad signal intensity alteration differentiate accelerated knee osteoarthritis. Rheumatology 58, 418–426 (2019).
pubmed: 30346594 doi: 10.1093/rheumatology/key305
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).
doi: 10.1186/s13075-015-0831-y
Zuk, P. A. et al. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 7, 211–228 (2001).
pubmed: 11304456 doi: 10.1089/107632701300062859
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).
pubmed: 23613363 doi: 10.1002/art.37908
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).
pubmed: 23360790 pmcid: 3672720 doi: 10.1186/ar4156
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).
pubmed: 27217345 pmcid: 4922848 doi: 10.5966/sctm.2015-0245
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).
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).
pubmed: 31020864 doi: 10.1080/03008207.2019.1611795
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).
pubmed: 26391756 doi: 10.1088/1748-6041/10/5/055011
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).
pubmed: 26516689 doi: 10.1111/aor.12565
Kouroupis, D., Kaplan, L. D. & Best, T. M. Human infrapatellar fat pad mesenchymal stem cells show immunomodulatory exosomal signatures. Sci. Rep. 12, 3609 (2022).
pubmed: 35246587 pmcid: 8897449 doi: 10.1038/s41598-022-07569-7
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).
pubmed: 29212384 doi: 10.1080/08916934.2017.1411481
Meurot, C. et al. Targeting the GLP-1/GLP-1R axis to treat osteoarthritis: A new opportunity? J. Orthop. Transl. 32, 121–129 (2022).
Daheshia, M. & Yao, J. Q. The interleukin 1beta pathway in the pathogenesis of osteoarthritis. J. Rheumatol. 35, 2306–2312 (2008).
pubmed: 18925684 doi: 10.3899/jrheum.080346
Akeson, G. & Malemud, C. J. A Role for Soluble IL-6 Receptor in Osteoarthritis. J. Funct. Morphol. Kinesiol. 2, 27 (2017).
pubmed: 29276788 doi: 10.3390/jfmk2030027
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).
pubmed: 33664374 pmcid: 7933151 doi: 10.1038/s41598-021-84582-2
Nagao, M. et al. Vascular Endothelial Growth Factor in Cartilage Development and Osteoarthritis. Sci. Rep. 7, 13027 (2017).
pubmed: 29026147 pmcid: 5638804 doi: 10.1038/s41598-017-13417-w
Yan, M., Zhang, J., Yang, H. & Sun, Y. The role of leptin in osteoarthritis. Medicine 97, e0257 (2018).
pubmed: 29620639 pmcid: 5902277 doi: 10.1097/MD.0000000000010257
Zhao, C. W. et al. An Update on the Emerging Role of Resistin on the Pathogenesis of Osteoarthritis. Mediators Inflamm. 1, 1532164 (2019).
Feng, X., Xiao, J. & Bai, L. Role of adiponectin in osteoarthritis. Front. cell developmental Biol. 10, 992764 (2022).
doi: 10.3389/fcell.2022.992764

Auteurs

Magnolia G Wang (MG)

Department of Biology, School of Arts and Sciences, Philadelphia, PA, 19104, USA.
Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, Philadelphia, PA, 19104, USA.

Patrick Seale (P)

Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, Philadelphia, PA, 19104, USA.
Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.

David Furman (D)

Center for AI and Data Science of Aging, Buck Institute for Research on Aging, Novato, CA, 94945, USA. DFurman@buckinstitute.org.
Stanford 1000 Immunomes Project, Stanford University, Stanford, CA, 94305, USA. DFurman@buckinstitute.org.
IIMT, Universidad Austral, Consejo Nacional de Investigaciones Científicas y Técnicas, Pilar, 29, Argentina. DFurman@buckinstitute.org.

Classifications MeSH