Single cell transcriptomics in human osteoarthritis synovium and in silico deconvoluted bulk RNA sequencing

Huang, Zeyu; Luo, Zeyu; Cai, Yong Rui; Chou, Ching‐Heng; Yao, Menglin; Pei, Fuxing; Kraus, Virginia B.; Zhou, Kai

doi:10.1016/j.joca.2021.12.007

Cited by 21 publications

(26 citation statements)

References 19 publications

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“…The 5 studies included in this review were all published between 2020 and 2022 ( Table 1 ). Three articles were published from the United States (United States) ( Tsai et al, 2020 ; Li and Zheng 2020 ; McCoy et al, 2020 ), one article was jointly published from Germany and the United Kingdom ( Steinberg et al, 2021 ), and one article jointly published from China and the United States ( Huang et al, 2022 ). The articles were either defined as a retrospective or prospective.…”

Section: Resultsmentioning

confidence: 99%

“…Three of the overlapping DEGs, APOD, TNFAIP6, and IL6 are all genes that have been found to regulate the pro-inflammatory pathway ( Li and Zheng 2020 ; McCoy et al, 2020 ; Steinberg et al, 2021 ; Huang et al, 2022 ). IL6 was differently expressed in 3 of the 5 studies and is a key contributor to modulating inflammation in both acute and chronic inflammation ( McCoy et al, 2020 ; Steinberg et al, 2021 ; Huang et al, 2022 ; Safran et al, 2022 ). IL6 has a crucial role in the pathology of OA, as it induces MMP13 and through pathway signaling reduces the sensitization of IGF1 ( Wiegertjes et al, 2020 ).…”

Section: Resultsmentioning

confidence: 99%

“…The two retrospective studies obtained their RNAseq data from the NCBI GEO DataSets ( https://www.ncbi.nlm.nih.gov/gds ), in which one used the data from United States Human OA subjects ( Li and Zheng 2020 ) and the other used Australian Human OA subjects ( Tsai et al, 2020 ). In the three prospective studies, one used a post-traumatic equine model, and two used synovial tissue obtained prior to arthroplasty of either the hip or knee in human subjects ( Steinberg et al, 2021 ; Huang et al, 2022 ).…”

Section: Resultsmentioning

confidence: 99%

“…The 8 DEGs that were represented in at least 2 studies were: MMP1, MMP2, MMP13, APOD, TNFAIP6, IL6, FCER1G, and IGF1. Three of the overlapping DEGs, APOD, TNFAIP6, and IL6 are all genes that have been found to regulate the pro-inflammatory pathway ( Li and Zheng 2020 ; McCoy et al, 2020 ; Steinberg et al, 2021 ; Huang et al, 2022 ). IL6 was differently expressed in 3 of the 5 studies and is a key contributor to modulating inflammation in both acute and chronic inflammation ( McCoy et al, 2020 ; Steinberg et al, 2021 ; Huang et al, 2022 ; Safran et al, 2022 ).…”

Section: Resultsmentioning

confidence: 99%

“…IGF1 was shown to be highly expressed having a role in the inflammation resolving pathway, as well as having a role in enhanced extracellular matrix production and inhibition of apoptosis in chondrocytes. ( McCoy et al, 2020 ; Wen et al, 2021 ; Huang et al, 2022 ). The gene MMP13 was represented in 3 of the 5 studies included.…”

Section: Resultsmentioning

confidence: 99%

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RNAseq of Osteoarthritic Synovial Tissues: Systematic Literary Review

2022

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Osteoarthritis (OA) is one of the most common causes of disability in aged people, and it is defined as a degenerative arthropathy, characterized by the disruption in joint tissue. The synovium plays a vital role in maintaining the health of the joint by supplying the nutrients to the surrounding tissues and the lubrication for joint movement. While it is well known that all the joint tissues are communicating and working together to provide a functioning joint, most studies on OA have been focused on bone and cartilage but much less about synovium have been reported. The purpose of this review was to investigate the current literature focused on RNA sequencing (RNAseq) of osteoarthritic synovial tissues to further understand the dynamic transcriptome changes occurring in this pivotal joint tissue. A total of 3 electronic databases (PubMed, CINHAL Complete, and Academic Complete) were systematically searched following PRISMA guidelines. The following criteria was used for inclusion: English language, free full text, between the period 2011–2022, size of sample (n > 10), study design being either retrospective or prospective, and RNAseq data of synovial tissue from OA subjects. From the initial search, 174 articles, 5 met all of our criteria and were selected for this review. The RNAseq analysis revealed several differentially expressed genes (DEGs) in synovial tissue. These genes are related to the inflammatory pathway and regulation of the extracellular matrix. The MMP family, particularly MMP13 was identified by three of the studies, indicating its important role in OA. IL6, a key contributor in the inflammation pathway, was also identified in 3 studies. There was a total of 8 DEGs, MMP13, MMP1, MMP2, APOD, IL6, TNFAIP6, FCER1G, and IGF1 that overlapped in 4 out of the 5 studies. One study focused on microbial RNA in the synovial tissue found that the microbes were differentially expressed in OA subjects too. These differentially expressed microbes have also been linked to the inflammatory pathway. Further investigation with more clinical gene profiling in synovial tissue of OA subjects is required to reveal the causation and progression, as well as aid in the development of new treatments.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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RNAseq of Osteoarthritic Synovial Tissues: Systematic Literary Review

2022

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Isolation of High‐Quality Total RNA from Small Animal Articular Cartilage for Next‐Generation Sequencing

et al. 2023

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Articular cartilage is characterized by a low density of chondrocytes surrounded by an abundant extracellular matrix (ECM) consisting of a dense mixture of collagens, proteoglycans, and glycosaminoglycans. Due to its low cellularity and high proteoglycan content, it is particularly challenging to extract highquality total RNA suitable for sensitive high-throughput downstream applications such as RNA sequencing (RNA-Seq). Available protocols for high-quality RNA isolation from articular chondrocytes are inconsistent, resulting in suboptimal yield and compromised quality. This poses a significant difficulty in the application of RNA-Seq to study the cartilage transcriptome. Current protocols rely either on dissociation of cartilage ECM by collagenase digestion or pulverizing cartilage using various methods prior to RNA extraction. However, protocols for cartilage processing vary significantly depending on the species and source of cartilage within the body. Protocols for isolating RNA from human or large mammal (e.g., horse or cattle) cartilage samples are available, but this is not the case for chicken cartilage, despite the species being extensively used in cartilage research. Here, we present two improved RNA isolation protocols based on pulverization of fresh articular cartilage using a cryogenic mill or on enzymatic digestion using 1.2% (w/v) collagenase II. Our protocols optimize the collection and tissue processing steps to minimize RNA degradation and enhance RNA purity. Our results show that RNA purified from chicken articular cartilage using these methods has appropriate quality for RNA-Seq experiments. The procedure is applicable for RNA extraction from cartilage from other species such as dog, cat, sheep, and goat. The workflow for RNA-Seq analysis is also described here.

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Enhancing Endogenous Hyaluronic Acid in Osteoarthritic Joints with an Anti‐Inflammatory Supramolecular Nanofiber Hydrogel Delivering HAS2 Lentivirus

Zhou,

Chen,

Qian

et al. 2024

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Osteoarthritis (OA) management remains challenging because of its intricate pathogenesis. Intra‐articular injections of drugs, such as glucocorticoids and hyaluronic acid (HA), have certain limitations, including the risk of joint infection, pain, and swelling. Hydrogel‐based therapeutic strategies have attracted considerable attention because of their enormous therapeutic potential. Herein, a supramolecular nanofiber hydrogel is developed using dexamethasone sodium phosphate (DexP) as a vector to deliver lentivirus‐encoding hyaluronan synthase 2 (HAS2) (HAS2@DexP‐Gel). During hydrogel degradation, HAS2 lentivirus and DexP molecules are slowly released. Intra‐articular injection of HAS2@DexP‐Gel promotes endogenous HA production and suppresses synovial inflammation. Additionally, HAS2@DexP‐Gel reduces subchondral bone resorption in the anterior cruciate ligament transection‐induced OA mice, attenuates cartilage degeneration, and delays OA progression. HAS2@DexP‐Gel exhibited good biocompatibility both in vitro and in vivo. The therapeutic mechanisms of the HAS2@DexP‐Gel are investigated using single‐cell RNA sequencing. HAS2@DexP‐Gel optimizes the microenvironment of the synovial tissue by modulating the proportion of synovial cell subpopulations and regulating the interactions between synovial fibroblasts and macrophages. The innovative nanofiber hydrogel, HAS2@DexP‐Gel, effectively enhances endogenous HA production while reducing synovial inflammation. This comprehensive approach holds promise for improving joint function, alleviating pain, and slowing OA progression, thereby providing significant benefits to patients.

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Single cell transcriptomics in human osteoarthritis synovium and in silico deconvoluted bulk RNA sequencing

Cited by 21 publications

References 19 publications

RNAseq of Osteoarthritic Synovial Tissues: Systematic Literary Review

RNAseq of Osteoarthritic Synovial Tissues: Systematic Literary Review

Isolation of High‐Quality Total RNA from Small Animal Articular Cartilage for Next‐Generation Sequencing

Enhancing Endogenous Hyaluronic Acid in Osteoarthritic Joints with an Anti‐Inflammatory Supramolecular Nanofiber Hydrogel Delivering HAS2 Lentivirus

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