AbstractOsteoarthritis (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.

摘要骨关节炎（OA）是最常见的关节炎形式，仅在美国，每年的医疗保健支出就接近1400亿美元。肥胖，衰老和关节损伤是OA发展和进展的主要危险因素，但导致病理的机制仍不清楚。

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.

新出现的证据表明，关节组织（包括关节内脂肪组织库）中的细胞失调和炎症可能导致疾病的严重程度。特别是，位于膝关节的髌下脂肪垫（IFP）为关节负荷提供了保护垫，它还分泌多种内分泌因子和炎性细胞因子（炎症），可以调节关节生理和疾病。

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..

软骨变性和OA相关疾病严重程度的相关性包括模型生物和人体研究中IFP的炎症和纤维化。在本文中，我们讨论了了解关节内脂肪组织在调节关节生物学和OA中的作用和调节方面的最新进展。。

IntroductionWith an economic burden of almost $140 billion1, osteoarthritis (OA) is the most prevalent joint disease and a major cause of pain and disability in adults, estimated to affect one in every seven persons in the US2. OA most commonly affects the knee joints, but also can affect the hand, hip, and spine3.

引言骨关节炎（OA）的经济负担接近1400亿美元1，是最普遍的关节疾病，也是成人疼痛和残疾的主要原因，估计在美国每七个人中就有一个人受到影响2。OA最常影响膝关节，但也会影响手，髋和脊柱3。

OA is characterized by progressive cartilage damage, osteophyte (bone spur) formation, meniscal degeneration, and low-grade synovial inflammation, resulting in deterioration and pain4. It can present as a monoarticular disease, but up to 50% of patients have multiple joints involved5.Aging is a major risk factor for OA, and as the world’s population ages, the global disease burden of OA is rising6.

OA的特征是进行性软骨损伤，骨赘（骨刺）形成，半月板变性和低度滑膜炎症，导致恶化和疼痛4。它可以表现为单关节疾病，但高达50%的患者涉及多个关节5。衰老是OA的主要危险因素，随着世界人口的老龄化，OA的全球疾病负担正在上升6。

Approximately 50% of symptomatic knee OA (KOA) patients are diagnosed by age 55, and greater than 75% are diagnosed by age 657. Aging is linked with elevated circulating levels of pro-inflammatory cytokines (inflammaging)8, which promote pathology of cartilage, synovium, and bone within the joint9,10.

大约50%的有症状膝关节OA（KOA）患者在55岁时被诊断出，超过75%的患者在657岁时被诊断出。衰老与促炎细胞因子（炎症）8的循环水平升高有关，促进关节内软骨，滑膜和骨骼的病理9,10。

This is coupled with the accumulation of senescent cells, which robustly secrete pro-inflammatory and disease-promoting factors (the senescence-associated secretory phenotype, SASP)11.Another risk factor that can severely impact OA pathology is obesity. It is believed that it does so by different mechanisms involving mechanical stress and tissue-derived inflammation.

这与衰老细胞的积累相结合，衰老细胞强烈分泌促炎和疾病促进因子（衰老相关分泌表型，SASP）11。另一个可能严重影响OA病理的危险因素是肥胖。据信，它是通过涉及机械应力和组织衍生炎症的不同机制实现的。

First, increased body weight puts excess stress on weight-bearing joints like the knee, which can lead to reduced mechanical function and injury12. Second, obesity can cause or exacerbate systemic inflammation and metabolic complications, promoting OA development13. Interestingly, obesity (and its link with aging) is associated with pathologic changes in joint tissues, including enlarged local adipose (fa.

首先，体重增加会给膝盖等负重关节带来过大的压力，这可能导致机械功能下降和受伤12。其次，肥胖可以引起或加剧全身炎症和代谢并发症，促进OA的发展13。有趣的是，肥胖（及其与衰老的联系）与关节组织的病理变化有关，包括局部脂肪（fa）增大。

Data Availability

数据可用性

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

数据共享不适用于本文，因为在当前研究期间没有生成或分析数据集。

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Download referencesAcknowledgementsWe would like to thank Hannah Bryce Ely, CMI for illustrations of the knee joint. We also extend our gratitude towards Carla Scanzello, M.D. Ph.D. of Perelman School of Medicine for her clinical insight provided on OA pain, progression, and fibrosis.

下载参考文献致谢我们要感谢CMI的HannahBryce Ely为膝关节提供的插图。我们还感谢佩雷尔曼医学院医学博士卡拉·斯坎泽洛（CarlaScanzello）对OA疼痛，进展和纤维化的临床见解。

This study was funded by a University Scholars Research Funding Award to M.G.W. and NIDDK grant DK123356 to P.S. The funders played no role in study design, data collection, analysis, and interpretation of data, or the writing of this manuscript.Author informationAuthors and AffiliationsDepartment of Biology, School of Arts and Sciences, Philadelphia, PA, 19104, USAMagnolia G.

这项研究由M.G.W.的大学学者研究资助奖和P.S的NIDDK拨款DK123356资助。资助者在研究设计，数据收集，分析和数据解释或撰写本手稿方面没有任何作用。作者信息作者和附属机构宾夕法尼亚州费城艺术与科学学院生物学系，19104，USAMGNOLIA G。

WangInstitute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, Philadelphia, PA, 19104, USAMagnolia G. Wang & Patrick SealeDepartment of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USAPatrick SealeCenter for AI and Data Science of Aging, Buck Institute for Research on Aging, Novato, CA, 94945, USADavid FurmanStanford 1000 Immunomes Project, Stanford University, Stanford, CA, 94305, USADavid FurmanIIMT, Universidad Austral, Consejo Nacional de Investigaciones Científicas y Técnicas, Pilar, 29, ArgentinaDavid FurmanAuthorsMagnolia G.

宾夕法尼亚州费城佩雷尔曼医学院糖尿病、肥胖与代谢研究所，宾夕法尼亚州费城，19104，USAMGNOLIA G.Wang&Patrick SealeDepartment of Cell and Development Biology，佩雷尔曼医学院，宾夕法尼亚大学，宾夕法尼亚州费城，19104，USAPrick SealeCenter for AI and Data Science of Aging，Buck Institute for Research on Aging，Novato，CA，94945，USADVID FurmanStanford 1000 Immunomes Project，Stanford University，Stanford，CA，94305，USADVID FURMAIMT，Universidad Austral，Consejo National de Investigaciones Cientíy Técnicas 29岁的皮拉尔（Pilar），阿根廷（ArgentinaDavid FurmanAuthorsMagnolia G.）。

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PubMed Google ScholarContributionsM.W.: Conception and design; collection and assembly of data; analysis and interpretation of the data; drafting of the article; critical revision of the article for important intellectual content; final approval of the article; obtaining of funding.

PubMed谷歌学术贡献。W、 ：概念和设计；数据的收集和汇编；数据的分析和解释；起草条款；对重要知识内容的文章进行批判性修订；物品的最终批准；获得资金。

D.F.: Critical revision of the article for important intellectual content; final approval of the article. P.S.: Critical revision of the article for important intellectual content; final approval of the article. All authors read and approved the final manuscript.Corresponding authorCorrespondence to.

D、 F.：对重要知识内容的文章进行批判性修订；文章的最终批准。P、 美国：对重要知识内容的文章进行了批判性修订；文章的最终批准。所有作者都阅读并批准了最终稿件。对应作者对应。

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Reprints and permissionsAbout this articleCite this articleWang, M.G., Seale, P. & Furman, D. The infrapatellar fat pad in inflammaging, knee joint health, and osteoarthritis.

转载和许可本文引用本文Wang，M.G.，Seale，P。＆Furman，D。炎症，膝关节健康和骨关节炎中的髌下脂肪垫。

npj Aging 10, 34 (2024). https://doi.org/10.1038/s41514-024-00159-zDownload citationReceived: 23 March 2024Accepted: 12 June 2024Published: 15 July 2024DOI: https://doi.org/10.1038/s41514-024-00159-zShare this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

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