Review
Biochemistry & Molecular Biology
Sebastian Braun, Frank Zaucke, Marco Brenneis, Anna E. Rapp, Patrizia Pollinger, Rebecca Sohn, Zsuzsa Jenei-Lanzl, Andrea Meurer
Summary: In recent years, there has been increasing research interest in the infrapatellar fat pad (IFP). It is believed to play a role in the development and progression of knee osteoarthritis (OA) through its interactions with the synovium, articular cartilage, and subchondral bone. While IFP is (partially) resected in most total knee arthroplasties (TKA), there is currently no clear guideline in favor of or against this practice.
Article
Immunology
Shuhe Ma, Kosaku Murakami, Rintaro Saito, Hiromu Ito, Koichi Murata, Kohei Nishitani, Motomu Hashimoto, Masao Tanaka, Masahi Taniguchi, Koji Kitagori, Shuji Akizuki, Ran Nakashima, Hajime Yoshifuji, Koichiro Ohmura, Akio Morinobu, Tsuneyo Mimori
Summary: This study identified differences in the quantity and quality of CD14-positive cells in the infrapatellar fat pads and subcutaneous fat tissues of OA and RA patients. Patients treated with bDMARDs showed a higher ratio of CD14(++)CD80(+) cells/CD14(++)CD163(+) cells in the IFP, indicating localized inflammation. This suggests that adipose tissue-derived innate immune cells could be a potential target for new therapeutic strategies in inflammatory joint diseases.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Engineering, Biomedical
Junjun Yang, Xin Wang, Yahan Fan, Xiongbo Song, Jiangyi Wu, Zhenlan Fu, Tao Li, Yang Huang, ZheXiong Tang, Shuo Meng, Na Liu, Jiajia Chen, Pingju Liu, Liu Yang, Xiaoyuan Gong, Cheng Chen
Summary: Intra-articular injection of tropoelastin (TE) improves the adhesion, migration, and chondrogenic differentiation of mesenchymal stem cells (MSCs) and enhances matrix synthesis of osteoarthritic chondrocytes (OACs). In vitro experiments demonstrate that TE enhances MSCs adhesion through activation of specific pathways. In vivo experiments show that intra-articular injection of TE-MSCs suspension increases MSCs survival rate and improves histology scores of joint tissues.
BIOACTIVE MATERIALS
(2022)
Article
Biochemistry & Molecular Biology
Peter Kreitmaier, Young-Chan Park, Diane Swift, Arthur Gilly, J. Mark Wilkinson, Eleftheria Zeggini
Summary: This study examines the DNA methylation profiles of infrapatellar fat pad and blood samples from osteoarthritis patients, revealing widespread epigenetic differences. The researchers produce the first genome-wide methylation quantitative trait locus map and provide insights into the molecular mechanisms of osteoarthritis.
HUMAN MOLECULAR GENETICS
(2023)
Article
Chemistry, Multidisciplinary
Bingyang Dai, Yuwei Zhu, Xu Li, Zuru Liang, Shunxiang Xu, Shian Zhang, Zhe Zhang, Shanshan Bai, Wenxue Tong, Mingde Cao, Ye Li, Xiaobo Zhu, Wei Liu, Yuantao Zhang, Liang Chang, Patrick Shu-hang Yung, Kevin Ki-wai Ho, Jiankun Xu, To Ngai, Ling Qin
Summary: The study investigates the role of infrapatellar fat pad (IPFP) in knee osteoarthritis (OA) progression and identifies dysregulated osteopontin (OPN) and integrin beta 3 signaling in OA specimens. The study demonstrates that IPFP-derived OPN plays a role in OA progression, including chondrocyte hypertrophy and IPFP fibrosis. An injectable nanogel, (RGD-)Nanogel/siRNA Cd61, is developed to target integrins and effectively alleviate cartilage degeneration and subchondral bone mass in OA mice.
Article
Chemistry, Multidisciplinary
Yumei Cao, Jianzhao Ruan, Jingliang Kang, Xiaoyu Nie, Weiren Lan, Guangfeng Ruan, Jia Li, Zhaohua Zhu, Weiyu Han, Su'an Tang, Changhai Ding
Summary: Infrapatellar fat pad (IPFP) is associated with the progression of knee osteoarthritis (OA), as it secretes small extracellular vesicles (sEVs) that promote cartilage destruction and cellular senescence. The let-7b-5p and let-7c-5p in IPFP-sEVs directly decrease the negative regulator of senescence, lamin B receptor (LBR). This study uncovers the function and mechanism of IPFP-sEVs in the progression of OA, providing a potential strategy for OA therapy.
Review
Biochemistry & Molecular Biology
Parviz Vahedi, Rana Moghaddamshahabi, Thomas J. Webster, Ayse Ceren Calikoglu Koyuncu, Elham Ahmadian, Wasim S. Khan, Ali Jimale Mohamed, Aziz Eftekhari
Summary: Cartilage damage is often difficult to repair, and current treatment strategies are inadequate. Autologous mesenchymal stem cells are considered a promising therapeutic approach for cartilage regeneration, as they possess robust cartilaginous production capacity and are easy to isolate and expand without causing morbidity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Orthopedics
Qin Ye, Dong He, Xiaonan Ding, Yajie Wang, Yuguo Wei, Jing Liu
Summary: This study evaluated the infrapatellar fat pad (IFP) in knee osteoarthritis (KOA) using radiomics and developed a radiomic signature for assessing IFP in KOA progression. The results showed that radiomic alterations in IFP were associated with the severity and structural abnormalities of KOA.
BMC MUSCULOSKELETAL DISORDERS
(2023)
Article
Cell Biology
Zuoqing Zhou, Su'an Tang, Xiaoyu Nie, Yiqun Zhang, Delong Li, Yang Zhao, Yumei Cao, Jianwen Yin, Tianyu Chen, Guangfeng Ruan, Zhaohua Zhu, Xiaochun Bai, Weiyu Han, Changhai Ding
Summary: This study demonstrates that osteoarthritic IPFP-derived fat-conditioned medium can induce ECM degradation in chondrocytes and cartilage explants, activate multiple signaling pathways, and ultimately lead to cartilage degradation and inflammation via the p38MAPK and ERK1/2 pathways. IL-1 beta and TNF-alpha play key roles in this process. Modulating the effects of IPFP on cartilage may be a promising strategy for knee osteoarthritis intervention.
INFLAMMATION RESEARCH
(2021)
Article
Multidisciplinary Sciences
Mutsuaki Edama, Tomofumi Otsuki, Hirotake Yokota, Ryo Hirabayashi, Chie Sekine, Sae Maruyama, Ikuo Kageyama
Summary: This study aimed to investigate the morphological characteristics of the infrapatellar fat pad (IFP) and its relationship with the degenerative grade of the patellar articular surface. The study found a negative correlation between the degenerative grade of the patellar articular surface and the volume of the IFP.
SCIENTIFIC REPORTS
(2022)
Article
Biophysics
Chiara Giulia Fontanella, Elisa Belluzzi, Assunta Pozzuoli, Marta Favero, Pietro Ruggieri, Veronica Macchi, Emanuele Luigi Carniel
Summary: The study aims to analyze the mechanical behavior of the infrapatellar fat pad (IFP) in end-stage osteoarthritis (OA) patients and found that the OA IFP is stiffer compared to other adipose tissues. Gender, BMI, and sample preparation were not found to significantly influence the mechanical characteristics of OA IFP.
JOURNAL OF BIOMECHANICS
(2022)
Article
Orthopedics
Ni Zeng, Tao Liao, Xin-Yuan Chen, Zhi-Peng Yan, Jie-Ting Li, Guo-Xin Ni
Summary: The response of the infrapatellar fat pad (IFP) to running is intensity dependent, with high-intensity running leading to increased fibrosis and vascularity. Low to medium intensity running may not cause significant changes in the IFP.
JOURNAL OF ORTHOPAEDIC SURGERY AND RESEARCH
(2021)
Article
Cell Biology
Benjamen T. O'Donnell, Tia A. Monjure, Sara Al-Ghadban, Clara J. Ives, Michael P. L'Ecuyer, Claire Rhee, Monica Romero-Lopez, Zhong Li, Stuart B. Goodman, Hang Lin, Rocky S. Tuan, Bruce A. Bunnell
Summary: This study explores the link between pre-diabetes and osteoarthritis, showing that pre-diabetic conditions can affect the characteristics of adipose stem cells in the infrapatellar fat pad, including their inflammatory gene expression and lipid hormone secretion. The findings suggest that the heightened systemic inflammation associated with untreated T2D may prime the adipose stem cells to exhibit enhanced anti-inflammatory characteristics, potentially influencing the onset and progression of osteoarthritis.
Article
Medicine, General & Internal
Elena Stocco, Elisa Belluzzi, Martina Contran, Rafael Boscolo-Berto, Edgardo Picardi, Diego Guidolin, Chiara Giulia Fontanella, Eleonora Olivotto, Giuseppe Filardo, Giulia Borile, Filippo Romanato, Roberta Ramonda, Pietro Ruggieri, Marta Favero, Andrea Porzionato, Raffaele De Caro, Veronica Macchi
Summary: The infrapatellar fat pad (IFP) plays an important role in knee osteoarthritis, with age affecting its tissue characteristics even in the absence of pathological conditions. Differences were observed between the young group and elderly group in terms of collagen III levels and adipocyte size. Additionally, aging was associated with a decrease in total collagen deposition in the IFP tissue.
FRONTIERS IN MEDICINE
(2021)
Article
Orthopedics
Yuan-Chao Sun, Pei-Hung Shen, Chih-Chien Wang, Hsin-Ya Liu, Chieh-Hua Lu, Sheng-Chiang Su, Jhih-Syuan Liu, Peng-Fei Li, Chia-Luen Huang, Li-Ju Ho, Yi-Jen Hung, Chien-Hsing Lee, Feng-Chih Kuo
Summary: This study aimed to explore the influence of age and body mass index (BMI) on the characteristics of infrapatellar fat pad (IFP) cells and determine the clinical potential of IFP-derived dedifferentiated fat cells (DFATs). The results showed that DFATs had superior chondrogenic and adipogenic abilities compared to stromal cells (SCs) in knee osteoarthritis (OA) patients who were old or of normal weight. RNA sequencing and Seahorse analysis indicated that the downregulation of eukaryotic initiation factor 2 (EIF2) signaling and enhanced mitochondrial function might contribute to the improved cellular biology of IFP-DFATs.
JOURNAL OF ORTHOPAEDIC TRANSLATION
(2023)
Article
Orthopedics
S. Zaki, M. M. Smith, S. M. Smith, C. B. Little
OSTEOARTHRITIS AND CARTILAGE
(2020)
Article
Rheumatology
Jamie Soul, Matthew J. Barter, Christopher B. Little, David A. Young
Summary: The study identified 459 genes modulated in animal models of OA, with ageing and post-traumatic models being the most prominent. Ninety-eight of the 143 genes genetically modulated more than once had a consistent effect on OA joint damage severity. By expanding existing annotations and prioritising promising therapeutic targets, the study validated the associations using the latest reported data.
ANNALS OF THE RHEUMATIC DISEASES
(2021)
Article
Orthopedics
Carina L. Blaker, Sanaa Zaki, Christopher B. Little, Elizabeth C. Clarke
Summary: This study in mice found that subcritical knee injury can lead to specific joint tissue pathologies (osteochondral lesions and progressive weakening of the ACL) and allodynic sensitization, indicating a predisposition for secondary critical injuries (such as ACL rupture) and an increased risk of PTOA onset and progression.
AMERICAN JOURNAL OF SPORTS MEDICINE
(2021)
Article
Biophysics
Carina L. Blaker, Dylan M. Ashton, Nathan Doran, Christopher B. Little, Elizabeth C. Clarke
Summary: Sex and joint injury play important roles in the onset and progression of osteoarthritis. This study evaluated passive anterior-posterior knee biomechanics in male and female mice, finding that joint laxity was comparable between sexes but joint stiffness was greater in females. The anterior-posterior joint mechanics were significantly affected by the loss of the ACL, regardless of the injury model used.
JOURNAL OF BIOMECHANICS
(2021)
Article
Cell & Tissue Engineering
Louise H. W. Kung, Lisa Sampurno, Christopher B. Little, Shireen R. Lamande, John F. Bateman
Summary: miR-26b is implicated in various human diseases, and a homozygous miR-26b stem-loop knockout human iPSC line has been generated and characterized in this study. This gene-edited iPSC line exhibits normal karyotype, pluripotency markers, and differentiation potential, making it valuable for investigating disease mechanisms and therapeutic strategies in vitro.
STEM CELL RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Sean T. Ryan, Elham Hosseini-Beheshti, Dinara Afrose, Xianting Ding, Binbin Xia, Georges E. Grau, Christopher B. Little, Lana McClements, Jiao Jiao Li
Summary: MSC-derived EVs have shown therapeutic potential for treating inflammation-related conditions and have demonstrated efficacy in studies. They can serve as anti-inflammatory and pro-regenerative agents for diseases like osteoarthritis, rheumatoid arthritis, and Alzheimer's disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Orthopedics
S. Zaki, C. L. Blaker, C. B. Little
Summary: Osteoarthritis is a disease with diverse phenotypes, and the selection and use of animal models in research should align with patient sub-types. This review discusses the importance of selecting animal models based on study objectives, alignment with sub-types, and available resources. It also proposes an experimental design checklist for choosing the optimal model.
OSTEOARTHRITIS AND CARTILAGE
(2022)
Review
Chemistry, Medicinal
Win Min Oo, Christopher Little, Vicky Duong, David J. Hunter
Summary: This review discusses the need for disease modifying drugs (DMOADs) for the management of osteoarthritis (OA), the classification of clinical phenotypes or molecular/mechanistic endotypes for targeted drug discovery, and summarizes the efficacy and safety of targeted drugs in Phase 2 and 3 clinical trials targeting cartilage-driven, bone-driven, and inflammation-driven endotypes. The reasons for failures in OA clinical trials and possible steps to overcome these barriers are also briefly presented.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2021)
Editorial Material
Orthopedics
E. M. Roos, M. A. Risberg, C. B. Little
OSTEOARTHRITIS AND CARTILAGE
(2021)
Review
Orthopedics
Y. Z. Lim, Y. Wang, M. Estee, J. Abidi, M. Udaya Kumar, S. M. Hussain, A. E. Wluka, C. B. Little, F. M. Cicuttini
Summary: Objective: This study systematically reviewed the potential disease-modifying effect of metformin in osteoarthritis based on evidence from pre-clinical and human studies. The results suggest that metformin has chondroprotective, immunomodulatory, and analgesic effects in osteoarthritis, supported by consistent findings in pre-clinical and human studies. Further high-quality clinical trials are needed to confirm these findings.
OSTEOARTHRITIS AND CARTILAGE
(2022)
Editorial Material
Cell & Tissue Engineering
C. B. Little, S. Zaki, C. L. Blaker, E. C. Clarke
BONE & JOINT RESEARCH
(2022)
Article
Orthopedics
Dylan M. Ashton, Carina L. Blaker, Nicholas Hartnell, Patrick Haubruck, Samantha A. Hefferan, Christopher B. Little, Elizabeth C. Clarke
Summary: This study investigated the mechanical properties of a range of human lower leg tendons and their relationship with donor age, sex, and height. The results showed significant differences in mechanical properties among different tendons, with relatively small effects of donor characteristics limited to specific tendons. The findings challenge the exclusion of donors aged >65 years in all tendon grafts, as age only negatively affected the properties of the Achilles tendon (maximum load).
AMERICAN JOURNAL OF SPORTS MEDICINE
(2023)
Editorial Material
Orthopedics
C. B. Little
OSTEOARTHRITIS AND CARTILAGE
(2023)
Article
Multidisciplinary Sciences
Jia Q. Ng, Toghrul H. Jafarov, Christopher B. Little, Tongtong Wang, Abdullah M. Ali, Yan Ma, Georgette A. Radford, Laura Vrbanac, Mari Ichinose, Samuel Whittle, David J. Hunter, Tamsin R. M. Lannagan, Nobumi Suzuki, Jarrad M. Goyne, Hiroki Kobayashi, Timothy C. Wang, David R. Haynes, Danijela Menicanin, Stan Gronthos, Daniel L. Worthley, Susan L. Woods, Siddhartha Mukherjee
Summary: Osteoarthritis is characterized by irreversible degeneration of articular cartilage. Gremlin 1 marks a bipotent cell population on the articular surface, which plays a crucial role in chondrogenic and osteogenic progenitor cells. These cells are affected by injury and aging, leading to the development of osteoarthritis.
NATURE COMMUNICATIONS
(2023)
Review
Engineering, Biomedical
Rouyan Chen, Jasmine Sarah Pye, Jiarong Li, Christopher B. Little, Jiao Jiao Li
Summary: Osteochondral defects result in damage to both articular cartilage and subchondral bone, leading to irreversible joint damage and a higher risk of osteoarthritis. Current treatments only address symptoms and are not curative, necessitating the development of tissue engineering solutions. Scaffold-based approaches, using biomaterials tailored to cartilage and bone properties, show promising results in regenerating osteochondral tissue and minimizing further degeneration.
BIOACTIVE MATERIALS
(2023)
