Cited by 59Osteoarthritis Treatment and MechanismsSingle-cell and spatial transcriptomicsBone and Joint Diseases

Single‐cell RNA sequencing in osteoarthritis

Open access
Gu, Yuyuan, Hu, Yan, Zhang, Hao, Wang, Sicheng, Xu, Ke, Su, Jiacan·2023·Cell Proliferation

Abstract

Osteoarthritis is a progressive and heterogeneous joint disease with complex pathogenesis. The various phenotypes associated with each patient suggest that better subgrouping of tissues associated with genotypes in different phases of osteoarthritis may provide new insights into the onset and progression of the disease. Recently, single‐cell RNA sequencing was used to describe osteoarthritis pathogenesis on a high‐resolution view surpassing traditional technologies. Herein, this review summarizes the microstructural changes in articular cartilage, meniscus, synovium and subchondral bone that are mainly due to crosstalk amongst chondrocytes, osteoblasts, fibroblasts and endothelial cells during osteoarthritis progression. Next, we focus on the promising targets discovered by single‐cell RNA sequencing and its potential applications in target drugs and tissue engineering. Additionally, the limited amount of research on the evaluation of bone‐related biomaterials is reviewed. Based on the pre‐clinical findings, we elaborate on the potential clinical values of single‐cell RNA sequencing for the therapeutic strategies of osteoarthritis. Finally, a perspective on the future development of patient‐centred medicine for osteoarthritis therapy combining other single‐cell multi‐omics technologies is discussed. This review will provide new insights into osteoarthritis pathogenesis on a cellular level and the field of applications of single‐cell RNA sequencing in personalized therapeutics for osteoarthritis in the future.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1111/cpr.13517

Cites

9 of 9 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Single-cell RNA sequencing, ATAC-seq, proteomics, and spatial transcriptomics provide unprecedented resolution of cellular heterogeneity, revealing distinct cell subpopulations and molecular signatures in joint tissues that drive pathogenesis.

    “Single-cell RNA sequencing, ATAC-seq, proteomics, and spatial transcriptomics provide an unprecedented resolution of cellular heterogeneity, revealing distinct cell subpopulations and molecular signatures in joint tissues that drive pathogenesis”

    From Biomarker-Guided Imaging and AI-Augmented Diagnosis of Degenerative Joint Disease (2025) · cites this paper as [160]

    Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured
  • Single-cell technologies offer potential cellular biomarkers for precise disease classification and targeted therapies.

    “offering potential cellular biomarkers for precise disease classification and targeted therapies [159,160].”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 171

  1. [1]Katz JN, Arant KR, Loeser RF. Diagnosis and treatment of hip and knee osteoarthritis: a review. JAMA. 2021; 325: 568‐ 578. 33560326 PMC8225295
  2. [2]Bijlsma JWJ, Berenbaum F, Lafeber FPJG. Osteoarthritis: an update with relevance for clinical practice. Lancet. 2011; 377: 2115‐ 2126. 21684382
  3. [3]Hunter DJ, Bierma‐Zeinstra S. Osteoarthritis. Lancet. 2019; 393: 1745‐ 1759. 31034380
  4. [4]Yuan C, Pan Z, Zhao K, et al. Classification of four distinct osteoarthritis subtypes with a knee joint tissue transcriptome atlas. Bone Res. 2020; 8: 38. 33298863 PMC7658991
  5. [5]Chen D, Shen J, Zhao W, et al. Osteoarthritis: toward a comprehensive understanding of pathological mechanism. Bone Res. 2017; 5: 16044. 28149655 PMC5240031
  6. [6]Castaneda S, Roman‐Blas JA, Largo R, Herrero‐Beaumont G. Osteoarthritis: a progressive disease with changing phenotypes. Rheumatology (Oxford). 2014; 53: 1‐ 3. 23878311
  7. [7]Shalek AK, Satija R, Shuga J, et al. Single‐cell RNA‐seq reveals dynamic paracrine control of cellular variation. Nature. 2014; 510: 363‐ 369. 24919153 PMC4193940
  8. [8]Haque A, Engel J, Teichmann SA, Lonnberg T. A practical guide to single‐cell RNA‐sequencing for biomedical research and clinical applications. Genome Med. 2017; 9: 75. 28821273 PMC5561556
  9. [9]Tang F, Barbacioru C, Wang Y, et al. mRNA‐Seq whole‐transcriptome analysis of a single cell. Nat Methods. 2009; 6: 377‐ 382. 19349980
  10. [10]Peng J, Sun BF, Chen CY, et al. Single‐cell RNA‐seq highlights intra‐tumoral heterogeneity and malignant progression in pancreatic ductal adenocarcinoma. Cell Res. 2019; 29: 725‐ 738. 31273297 PMC6796938
  11. [11]Jia Q, Chu H, Jin Z, Long H, Zhu B. High‐throughput single‐сell sequencing in cancer research. Signal Transduct Target Ther. 2022; 7: 145. PMC9065032 35504878
  12. [12]Hwang B, Lee JH, Bang D. Single‐cell RNA sequencing technologies and bioinformatics pipelines. Exp Mol Med. 2018; 50: 1‐ 14. PMC6082860 30089861
  13. [13]Jindal A, Gupta P, Jayadeva, Sengupta D. Discovery of rare cells from voluminous single cell expression data. Nat Commun. 2018; 9(1): 4719. 30413715 PMC6226447
  14. [15]Deng Q, Ramsköld D, Reinius B, Sandberg R. Single‐cell RNA‐seq reveals dynamic, random monoallelic gene expression in mammalian cells. Science. 2014; 343: 193‐ 196. 24408435
  15. [16]Greenblatt MB, Ono N, Ayturk UM, Debnath S, Lalani S. The Unmixing problem: a guide to applying single‐cell RNA sequencing to bone. J Bone Miner Res. 2019; 34: 1207‐ 1219. 31336008 PMC6658136
  16. [17]Fang C, Guo JW, Wang YJ, et al. Diterbutyl phthalate attenuates osteoarthritis in ACLT mice via suppressing ERK/c‐fos/NFATc1 pathway, and subsequently inhibiting subchondral osteoclast fusion. Acta Pharmacol Sin. 2022; 43: 1299‐ 1310. 34381182 PMC9061820
  17. [18]Mei Z, Dong X, Qian Y, et al. Association between the metabolome and bone mineral density in a Chinese population. EBioMedicine. 2020; 62: 103111. 33186808 PMC7670189
  18. [19]Glyn‐Jones S, Palmer AJR, Agricola R, et al. Osteoarthritis. Lancet. 2015; 386: 376‐ 387. 25748615
  19. [20]Papalexi E, Satija R. Single‐cell RNA sequencing to explore immune cell heterogeneity. Nat Rev Immunol. 2018; 18: 35‐ 45. 28787399
  20. [21]Nguyen A, Khoo WH, Moran I, Croucher PI, Phan TG. Single cell RNA sequencing of rare immune cell populations. Front Immunol. 2018; 9: 1553. 30022984 PMC6039576
  21. [22]Mereu E, Lafzi A, Moutinho C, et al. Benchmarking single‐cell RNA‐sequencing protocols for cell atlas projects. Nat Biotechnol. 2020; 38: 747‐ 755. 32518403
  22. [23]Paik DT, Cho S, Tian L, Chang HY, Wu JC. Single‐cell RNA sequencing in cardiovascular development, disease and medicine. Nat Rev Cardiol. 2020; 17: 457‐ 473. 32231331 PMC7528042
  23. [25]O'Flanagan CH, Campbell KR, Zhang AW, et al. Dissociation of solid tumor tissues with cold active protease for single‐cell RNA‐seq minimizes conserved collagenase‐associated stress responses. Genome Biol. 2019; 20: 210. 31623682 PMC6796327
  24. [26]Zhao XM, Cui LS, Hao HS, et al. Transcriptome analyses of inner cell mass and trophectoderm cells isolated by magnetic‐activated cell sorting from bovine blastocysts using single cell RNA‐seq. reproduction in domestic animals =. Zuchthygiene. 2016; 51: 726‐ 735. 27440443
  25. [27]Kulkarni A, Anderson AG, Merullo DP, Konopka G. Beyond bulk: a review of single cell transcriptomics methodologies and applications. Curr Opin Biotechnol. 2019; 58: 129‐ 136. 30978643 PMC6710112
  26. [28]Citri A, Pang ZP, Südhof TC, Wernig M, Malenka RC. Comprehensive qPCR profiling of gene expression in single neuronal cells. Nat Protoc. 2011; 7: 118‐ 127. 22193304 PMC4377330
  27. [29]Nichterwitz S, Chen G, Aguila Benitez J, et al. Laser capture microscopy coupled with smart‐seq2 for precise spatial transcriptomic profiling. Nat Commun. 2016; 7: 12139. 27387371 PMC4941116
  28. [30]Bendall SC, Nolan GP, Roederer M, Chattopadhyay PK. A deep profiler's guide to cytometry. Trends Immunol. 2012; 33: 323‐ 332. 22476049 PMC3383392
  29. [31]Ayturk U. RNA‐seq in skeletal biology. Curr Osteoporos Rep. 2019; 17: 178‐ 185. 31093870
  30. [32]Debnath S, Yallowitz AR, McCormick J, et al. Discovery of a periosteal stem cell mediating intramembranous bone formation. Nature. 2018; 562: 133‐ 139. 30250253 PMC6193396
  31. [33]Takahashi A, Nagata M, Gupta A, et al. Autocrine regulation of mesenchymal progenitor cell fates orchestrates tooth eruption. Proc Natl Acad Sci U S A. 2019; 116: 575‐ 580. 30509999 PMC6329940
  32. [34]Chen TN, Gupta A, Zalavadia MD, Streets A. μCB‐seq: microfluidic cell barcoding and sequencing for high‐resolution imaging and sequencing of single cells. Lab Chip. 2020; 20: 3899‐ 3913. 32931539 PMC8256654
  33. [35]Svensson V. Droplet scRNA‐seq is not zero‐inflated. Nat Biotechnol. 2020; 38: 147‐ 150. 31937974
  34. [36]Stott SL, Lee RJ, Nagrath S, et al. Isolation and characterization of circulating tumor cells from patients with localized and metastatic prostate cancer. Sci Transl Med. 2010; 2: 25ra23. PMC3141292 20424012
  35. [37]Hashimshony T, Senderovich N, Avital G, et al. CEL‐Seq2: sensitive highly‐multiplexed single‐cell RNA‐Seq. Genome Biol. 2016; 17: 77. 27121950 PMC4848782
  36. [38]Mary P, Dauphinot L, Bois N, Potier MC, Studer V, Tabeling P. Analysis of gene expression at the single‐cell level using microdroplet‐based microfluidic technology. Biomicrofluidics. 2011; 5: 24109. 21716808 PMC3124518
  37. [39]Machado L, Esteves de Lima J, Fabre O, et al. In situ fixation redefines quiescence and early activation of skeletal muscle stem cells. Cell Rep. 2017; 21: 1982‐ 1993. 29141227
  38. [40]Buenrostro JD, Wu B, Litzenburger UM, et al. Single‐cell chromatin accessibility reveals principles of regulatory variation. Nature. 2015; 523: 486‐ 490. 26083756 PMC4685948
  39. [41]Kim TH, Zhou X, Chen M. Demystifying “drop‐outs” in single‐cell UMI data. Genome Biol. 2020; 21: 196. 32762710 PMC7412673
  40. [43]Mamanova L, Miao Z, Jinat A, Ellis P, Shirley L, Teichmann SA. High‐throughput full‐length single‐cell RNA‐seq automation. Nat Protoc. 2021; 16: 2886‐ 2915. 33990801
  41. [44]Wang X, He Y, Zhang Q, Ren X, Zhang Z. Direct comparative analyses of 10X genomics chromium and smart‐seq2. Genomics Proteomics Bioinformatics. 2021; 19: 253‐ 266. 33662621 PMC8602399
  42. [45]Butler A, Hoffman P, Smibert P, Papalexi E, Satija R. Integrating single‐cell transcriptomic data across different conditions, technologies, and species. Nat Biotechnol. 2018; 36: 411‐ 420. 29608179 PMC6700744
  43. [46]Huang ZY, Luo ZY, Cai YR, et al. Single cell transcriptomics in human osteoarthritis synovium and in silico deconvoluted bulk RNA sequencing. Osteoarthr Cartil. 2022; 30: 475‐ 480. PMC10097426 34971754
  44. [47]Barile M, Imaz‐Rosshandler I, Inzani I, et al. Coordinated changes in gene expression kinetics underlie both mouse and human erythroid maturation. Genome Biol. 2021; 22: 197. 34225769 PMC8258993
  45. [48]Kolodziejczyk AA, Kim JK, Svensson V, Marioni JC, Teichmann SA. The technology and biology of single‐cell RNA sequencing. Mol Cell. 2015; 58: 610‐ 620. 26000846
  46. [49]Yajun W, Jin C, Zhengrong G, et al. Betaine attenuates osteoarthritis by inhibiting Osteoclastogenesis and angiogenesis in subchondral bone. Front Pharmacol. 2021; 12: 723988. 34658862 PMC8511433
  47. [50]Chang SH, Mori D, Kobayashi H, et al. Excessive mechanical loading promotes osteoarthritis through the gremlin‐1‐NF‐κB pathway. Nat Commun. 2019; 10: 1442. 30926814 PMC6441020
  48. [51]Berenbaum F. Deep phenotyping of osteoarthritis: a step forward. Ann Rheum Dis. 2019; 78: 3‐ 5. 30154088
  49. [52]Prein C, Warmbold N, Farkas Z, Schieker M, Aszodi A, Clausen‐Schaumann H. Structural and mechanical properties of the proliferative zone of the developing murine growth plate cartilage assessed by atomic force microscopy. Matrix Biol. 2016; 50: 1‐ 15. 26454027
  50. [53]Ji Q, Zheng Y, Zhang G, et al. Single‐cell RNA‐seq analysis reveals the progression of human osteoarthritis. Ann Rheum Dis. 2019; 78: 100‐ 110. 30026257 PMC6317448
  51. [54]Chen Y, Yu Y, Wen Y, et al. A high‐resolution route map reveals distinct stages of chondrocyte dedifferentiation for cartilage regeneration. Bone Res. 2022; 10: 38. 35477573 PMC9046296
  52. [55]Jeon J, Oh H, Lee G, et al. Cytokine‐like 1 knock‐out mice (Cytl1−/−) show normal cartilage and bone development but exhibit augmented osteoarthritic cartilage destruction. J Biol Chem. 2011; 286: 27206‐ 27213. 21652695 PMC3149314
  53. [56]Baboolal TG, Mastbergen SC, Jones E, Calder SJ, Lafeber FP, McGonagle D. Synovial fluid hyaluronan mediates MSC attachment to cartilage, a potential novel mechanism contributing to cartilage repair in osteoarthritis using knee joint distraction. Ann Rheum Dis. 2016; 75: 908‐ 915. 25948596 PMC4853581
  54. [57]Sebastian A, Murugesh DK, Mendez ME, et al. Global gene expression analysis identifies age‐related differences in knee joint transcriptome during the development of post‐traumatic osteoarthritis in mice. Int J Mol Sci. 2020; 21(1):364. PMC6982134 31935848
  55. [58]Wang X, Ning Y, Zhang P, et al. Comparison of the major cell populations among osteoarthritis, Kashin‐Beck disease and healthy chondrocytes by single‐cell RNA‐seq analysis. Cell Death Dis. 2021; 12: 551. 34045450 PMC8160352
  56. [59]Szychlinska MA, Trovato FM, Di Rosa M, et al. Co‐expression and Co‐localization of cartilage glycoproteins CHI3L1 and Lubricin in osteoarthritic cartilage: morphological, Immunohistochemical and gene expression profiles. Int J Mol Sci. 2016; 17: 359. 26978347 PMC4813220
  57. [60]Li H, Yang HH, Sun ZG, Tang HB, Min JK. Whole‐transcriptome sequencing of knee joint cartilage from osteoarthritis patients. Bone Joint Res. 2019; 8: 290‐ 303. 31463037 PMC6691371
  58. [61]Park S, Arai Y, Bello A, et al. SPRY4 acts as an indicator of osteoarthritis severity and regulates chondrocyte hypertrophy and ECM protease expression. NPJ Regenerative Med. 2021; 6: 56. PMC8448831 34535669
  59. [62]van der Kraan PM, van den Berg WB. Chondrocyte hypertrophy and osteoarthritis: role in initiation and progression of cartilage degeneration? Osteoarthr Cartil. 2012; 20: 223‐ 232. 22178514
  60. [63]Bertrand J, Kräft T, Gronau T, et al. BCP crystals promote chondrocyte hypertrophic differentiation in OA cartilage by sequestering Wnt3a. Ann Rheum Dis. 2020; 79: 975‐ 984. 32371389
  61. [64]He CP, Jiang XC, Chen C, et al. The function of lncRNAs in the pathogenesis of osteoarthritis. Bone Joint Res. 2021; 10: 122‐ 133. 33560158 PMC7937410
  62. [65]Li X, Liao Z, Deng Z, Chen N, Zhao L. lncRNACombining bulk and single‐cell RNA‐sequencing data to reveal gene expression pattern of chondrocytes in the osteoarthritic knee. Bioengineered. 2021; 12: 997‐ 1007. 33749514 PMC8806218
  63. [66]Cao L, Weng W, Chen X, et al. Promotion of in vivo degradability, vascularization and osteogenesis of calcium sulfate‐based bone cements containing nanoporous lithium doping magnesium silicate. Int J Nanomedicine. 2017; 12: 1341‐ 1352. 28260883 PMC5325137
  64. [67]Rim YA, Nam Y, Ju JH. The role of chondrocyte hypertrophy and senescence in osteoarthritis initiation and progression. Int J Mol Sci. 2020; 21(7):2358. PMC7177949 32235300
  65. [68]Peng Z, Sun H, Bunpetch V, et al. The regulation of cartilage extracellular matrix homeostasis in joint cartilage degeneration and regeneration. Biomaterials. 2021; 268: 120555. 33285440
  66. [69]Chan DD, Li J, Luo W, Predescu DN, Cole BJ, Plaas A. Pirfenidone reduces subchondral bone loss and fibrosis after murine knee cartilage injury. J Orthop Res. 2018; 36: 365‐ 376. 28646530 PMC5742076
  67. [70]Chou CH, Jain V, Gibson J, et al. Synovial cell cross‐talk with cartilage plays a major role in the pathogenesis of osteoarthritis. Sci Rep. 2020; 10: 10868. 32616761 PMC7331607
  68. [71]Tsolis KC, Bei ES, Papathanasiou I, et al. Comparative proteomic analysis of hypertrophic chondrocytes in osteoarthritis. Clin Proteomics. 2015; 12: 12. 25945082 PMC4415313
  69. [72]Li C, Luo J, Xu X, et al. Single cell sequencing revealed the underlying pathogenesis of the development of osteoarthritis. Gene. 2020; 757: 144939. 32640306
  70. [73]Nardone G, Oliver‐De La Cruz J, Vrbsky J, et al. YAP regulates cell mechanics by controlling focal adhesion assembly. Nat Commun. 2017; 8: 15321. 28504269 PMC5440673
  71. [74]Prasadam I, Farnaghi S, Feng JQ, et al. Impact of extracellular matrix derived from osteoarthritis subchondral bone osteoblasts on osteocytes: role of integrinβ1 and focal adhesion kinase signaling cues. Arthritis Res Ther. 2013; 15: R150. 24289792 PMC3978998
  72. [75]Kennedy D, Mnich K, Oommen D, et al. HSPB1 facilitates ERK‐mediated phosphorylation and degradation of BIM to attenuate endoplasmic reticulum stress‐induced apoptosis. Cell Death Dis. 2017; 8: e3026. 29048431 PMC5596589
  73. [76]Lv Z, Han J, Li J, et al. Single cell RNA‐seq analysis identifies ferroptotic chondrocyte cluster and reveals TRPV1 as an anti‐ferroptotic target in osteoarthritis. EBioMedicine. 2022; 84: 104258. 36137413 PMC9494174
  74. [77]Poulsen RC, Hearn JI, Dalbeth N. The circadian clock: a central mediator of cartilage maintenance and osteoarthritis development? Rheumatology (Oxford). 2021; 60: 3048‐ 3057. 33630038
  75. [78]Lee KI, Choi S, Matsuzaki T, et al. FOXO1 and FOXO3 transcription factors have unique functions in meniscus development and homeostasis during aging and osteoarthritis. Proc Natl Acad Sci U S A. 2020; 117: 3135‐ 3143. 31980519 PMC7022148
  76. [79]Wang C, Shen J, Ying J, Xiao D, O'Keefe RJ. FoxO1 is a crucial mediator of TGF‐β/TAK1 signaling and protects against osteoarthritis by maintaining articular cartilage homeostasis. Proc Natl Acad Sci U S A. 2020; 117: 30488‐ 30497. 33199631 PMC7720227
  77. [80]Jiang Y, Tuan RS. Origin and function of cartilage stem/progenitor cells in osteoarthritis. Nat Rev Rheumatol. 2015; 11: 206‐ 212. 25536487 PMC5413931
  78. [81]Wang F, Guo J, Wang S, et al. B‐cell lymphoma‐3 controls mesenchymal stem cell commitment and senescence during skeletal aging. Clin Transl Med. 2022; 12: e955. 35804493 PMC9270574
  79. [82]Scanzello CR, Goldring SR. The role of synovitis in osteoarthritis pathogenesis. Bone. 2012; 51: 249‐ 257. 22387238 PMC3372675
  80. [83]Wang D, Chai XQ, Hu SS, Pan F. Joint synovial macrophages as a potential target for intra‐articular treatment of osteoarthritis‐related pain. Osteoarthr Cartil. 2022; 30: 406‐ 415. 34861384
  81. [84]Zhang F, Wei K, Slowikowski K, et al. Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single‐cell transcriptomics and mass cytometry. Nat Immunol. 2019; 20: 928‐ 942. 31061532 PMC6602051
  82. [85]Nanus DE, Badoume A, Wijesinghe SN, et al. Synovial tissue from sites of joint pain in knee osteoarthritis patients exhibits a differential phenotype with distinct fibroblast subsets. EBioMedicine. 2021; 72: 103618. 34628351 PMC8511845
  83. [86]Pethő Z, Tanner MR, Tajhya RB, et al. Different expression of β subunits of the KCa1.1 channel by invasive and non‐invasive human fibroblast‐like synoviocytes. Arthritis Res Ther. 2016; 18: 103. 27165430 PMC4863321
  84. [87]Thomson CA, van de Pavert SA, Stakenborg M, et al. Expression of the atypical chemokine receptor ACKR4 identifies a novel population of intestinal submucosal fibroblasts that preferentially expresses endothelial cell regulators. J Immunol. 2018; 201: 215‐ 229. 29760193 PMC6013047
  85. [88]Wu Z, Shou L, Wang J, Xu X. Identification of the key gene and pathways associated with osteoarthritis via single‐cell RNA sequencing on synovial fibroblasts. Medicine (Baltimore). 2020; 99: e21707. 32872047 PMC7437759
  86. [89]Aladal M, You W, Huang R, et al. Insights into the implementation of fibronectin 1 in the cartilage tissue engineering. Biomed Pharmacother. 2022; 148: 112782. 35248846
  87. [90]Schröder A, Nazet U, Muschter D, Grässel S, Proff P, Kirschneck C. Impact of mechanical load on the expression profile of synovial fibroblasts from patients with and without osteoarthritis. Int J Mol Sci. 2019; 20(3):585. PMC6387339 30704030
  88. [91]Cai S, Ming B, Ye C, et al. Similar transition processes in synovial fibroblasts from rheumatoid arthritis and osteoarthritis: a single‐cell study. J Immunol Res. 2019; 2019: 4080735. 31428656 PMC6681591
  89. [92]Bondeson J, Wainwright SD, Lauder S, Amos N, Hughes CE. The role of synovial macrophages and macrophage‐produced cytokines in driving aggrecanases, matrix metalloproteinases, and other destructive and inflammatory responses in osteoarthritis. Arthritis Res Ther. 2006; 8: R187. 17177994 PMC1794533
  90. [93]Culemann S, Grüneboom A, Nicolás‐Ávila J, et al. Locally renewing resident synovial macrophages provide a protective barrier for the joint. Nature. 2019; 572: 670‐ 675. 31391580 PMC6805223
  91. [94]Zhou J, Zhao Z, He C, et al. Single‐cell transcriptome analysis profile of meniscal tissue macrophages in human osteoarthritis. J Immunol Res. 2020; 2020: 8127281. 32775469 PMC7407017
  92. [95]Wijesinghe SN, Badoume A, Nanus DE, et al. Obesity defined molecular endotypes in the synovium of patients with osteoarthritis provides a rationale for therapeutic targeting of fibroblast subsets. Clin Transl Med. 2023; 13: e1232. 37006170 PMC10068310
  93. [97]Englund M, Roemer FW, Hayashi D, Crema MD, Guermazi A. Meniscus pathology, osteoarthritis and the treatment controversy. Nat Rev Rheumatol. 2012; 8: 412‐ 419. 22614907
  94. [98]Rai MF, Brophy RH, Rosen V. Molecular biology of meniscus pathology: lessons learned from translational studies and mouse models. J Orthop Res. 2020; 38: 1895‐ 1904. 32068295 PMC7802285
  95. [99]Brophy RH, Zhang B, Cai L, Wright RW, Sandell LJ, Rai MF. Transcriptome comparison of meniscus from patients with and without osteoarthritis. Osteoarthr Cartil. 2018; 26: 422‐ 432. PMC6007850 29258882
  96. [100]Sun H, Wen X, Li H, et al. Single‐cell RNA‐seq analysis identifies meniscus progenitors and reveals the progression of meniscus degeneration. Ann Rheum Dis. 2020; 79: 408‐ 417. 31871141 PMC7034356
  97. [101]Xue X, Hu Y, Wang S, Chen X, Jiang Y, Su J. Fabrication of physical and chemical crosslinked hydrogels for bone tissue engineering. Bioact Mater. 2022; 12: 327‐ 339. 35128180 PMC8784310
  98. [102]Sun H, Zhang W, Liu F, et al. Single‐cell RNA sequencing reveals the cell types heterogenicity of human discoid lateral meniscus cells. J Cell Physiol. 2022; 237: 2469‐ 2477. 35220586
  99. [103]Chang JC, Christiansen BA, Murugesh DK, et al. SOST/Sclerostin improves posttraumatic osteoarthritis and inhibits MMP2/3 expression after injury. J Bone Miner Res. 2018; 33: 1105‐ 1113. 29377313 PMC6033030
  100. [104]Zhang Y, Li S, Jin P, et al. Dual functions of microRNA‐17 in maintaining cartilage homeostasis and protection against osteoarthritis. Nat Commun. 2022; 13: 2447. 35508470 PMC9068604
  101. [105]Mapp PI, Walsh DA. Mechanisms and targets of angiogenesis and nerve growth in osteoarthritis. Nat Rev Rheumatol. 2012; 8: 390‐ 398. 22641138
  102. [106]Lu D, Wei J, Chen J, et al. Apelin alleviates meniscus endothelial cell apoptosis in osteoarthritis. Dis Markers. 2022; 2022: 3556372. 35069930 PMC8777459
  103. [107]Hu W, Chen Y, Dou C, Dong S. Microenvironment in subchondral bone: predominant regulator for the treatment of osteoarthritis. Ann Rheum Dis. 2021; 80: 413‐ 422. 33158879 PMC7958096
  104. [109]Wang L, Zhang H, Wang S, Chen X, Su J. Bone marrow adipocytes: a critical player in the bone marrow microenvironment. Front Cell Dev Biol. 2021; 9: 770705. 34912805 PMC8667222
  105. [110]Li J, Yin Z, Huang B, Xu K, Su J. Stat3 signaling pathway: a future therapeutic target for bone‐related diseases. Front Pharmacol. 2022; 13: 897539. 35548357 PMC9081430
  106. [111]Tuerlings M, van Hoolwerff M, Houtman E, et al. RNA sequencing reveals interacting key determinants of osteoarthritis acting in subchondral bone and articular cartilage: identification of IL11 and CHADL as attractive treatment targets. Arthritis Rheumatol. 2021; 73: 789‐ 799. 33258547 PMC8252798
  107. [112]Kuliwaba JS, Findlay DM, Atkins GJ, Forwood MR, Fazzalari NL. Enhanced expression of osteocalcin mRNA in human osteoarthritic trabecular bone of the proximal femur is associated with decreased expression of interleukin‐6 and interleukin‐11 mRNA. J Bone Miner Res. 2000; 15: 332‐ 341. 10703936
  108. [113]Hu Y, Cui J, Liu H, et al. Single‐cell RNA‐sequencing analysis reveals the molecular mechanism of subchondral bone cell heterogeneity in the development of osteoarthritis. RMD Open. 2022; 8: e002314.
  109. [114]Song H, Li X, Zhao Z, et al. Reversal of osteoporotic activity by endothelial cell‐secreted bone targeting and biocompatible exosomes. Nano Lett. 2019; 19: 3040‐ 3048. 30968694
  110. [115]Peng Y, Wu S, Li Y, Crane JL. Type H blood vessels in bone modeling and remodeling. Theranostics. 2020; 10: 426‐ 436. 31903130 PMC6929606
  111. [116]Hu Y, Li X, Zhi X, et al. RANKL from bone marrow adipose lineage cells promotes osteoclast formation and bone loss. EMBO Rep. 2021; 22: e52481. 34121311 PMC8406405
  112. [117]Chen X, Zhi X, Wang J, Su J. RANKL signaling in bone marrow mesenchymal stem cells negatively regulates osteoblastic bone formation. Bone Res. 2018; 6: 34. 30510839 PMC6255918
  113. [118]Zhen G, Cao X. Targeting TGFβ signaling in subchondral bone and articular cartilage homeostasis. Trends Pharmacol Sci. 2014; 35: 227‐ 236. 24745631 PMC4058854
  114. [119]Sun P, He L, Jia K, et al. Regulation of body length and bone mass by Gpr126/Adgrg6. Sci Adv. 2020; 6: eaaz0368. 32219165 PMC7083604
  115. [120]Van Spil WE, Kubassova O, Boesen M, Bay‐Jensen AC, Mobasheri A. Osteoarthritis phenotypes and novel therapeutic targets. Biochem Pharmacol. 2019; 165: 41‐ 48. 30831073
  116. [121]Mao L, Wu W, Wang M, et al. Targeted treatment for osteoarthritis: drugs and delivery system. Drug Deliv. 2021; 28: 1861‐ 1876. 34515606 PMC8439249
  117. [122]Zhou D, Zhang H, Xue X, et al. Safety evaluation of natural drugs in chronic skeletal disorders: a literature review of clinical trials in the past 20 years. Front Pharmacol. 2021; 12: 801287. 35095508 PMC8793129
  118. [123]Robinson WH, Lepus CM, Wang Q, et al. Low‐grade inflammation as a key mediator of the pathogenesis of osteoarthritis. Nat Rev Rheumatol. 2016; 12: 580‐ 592. 27539668 PMC5500215
  119. [124]Latourte A, Kloppenburg M, Richette P. Emerging pharmaceutical therapies for osteoarthritis. Nat Rev Rheumatol. 2020; 16: 673‐ 688. 33122845
  120. [125]Chen Y, Wu X, Li J, Jiang Y, Xu K, Su J. Bone‐targeted nanoparticle drug delivery system: An emerging strategy for bone‐related disease. Front Pharmacol. 2022; 13: 909408. 35712701 PMC9195145
  121. [126]Hu Y, Li X, Zhang Q, et al. Exosome‐guided bone targeted delivery of Antagomir‐188 as an anabolic therapy for bone loss. Bioact Mater. 2021; 6: 2905‐ 2913. 33718671 PMC7917458
  122. [127]Ren X, Liu H, Wu X, Weng W, Wang X, Su J. Reactive oxygen species (ROS)‐responsive biomaterials for the treatment of bone‐related diseases. Front Bioeng Biotechnol. 2021; 9: 820468. 35087811 PMC8787194
  123. [128]Fu W, Hettinghouse A, Chen Y, et al. 14‐3‐3 epsilon is an intracellular component of TNFR2 receptor complex and its activation protects against osteoarthritis. Ann Rheum Dis. 2021; 80: 1615‐ 1627. 34226187 PMC8595573
  124. [129]Zhang Y, Guo W, Wang M, et al. Co‐culture systems‐based strategies for articular cartilage tissue engineering. J Cell Physiol. 2018; 233: 1940‐ 1951. 28548713
  125. [130]Harrell CR, Markovic BS, Fellabaum C, Arsenijevic A, Volarevic V. Mesenchymal stem cell‐based therapy of osteoarthritis: current knowledge and future perspectives. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie. 2019; 109: 2318‐ 2326. 30551490
  126. [131]McGonagle D, Baboolal TG, Jones E. Native joint‐resident mesenchymal stem cells for cartilage repair in osteoarthritis. Nat Rev Rheumatol. 2017; 13: 719‐ 730. 29118440
  127. [132]Xue K, Zhang X, Gao Z, Xia W, Qi L, Liu K. Cartilage progenitor cells combined with PHBV in cartilage tissue engineering. J Transl Med. 2019; 17: 104. 30925884 PMC6441183
  128. [133]Zhang S, Hamid MR, Wang T, et al. RSK‐3 promotes cartilage regeneration via interacting with rpS6 in cartilage stem/progenitor cells. Theranostics. 2020; 10: 6915‐ 6927. 32550912 PMC7295041
  129. [134]Delplace V, Boutet MA, Le Visage C, Maugars Y, Guicheux J, Vinatier C. Osteoarthritis: from upcoming treatments to treatments yet to come. Joint Bone Spine. 2021; 88: 105206. 33962030
  130. [135]Hodgkinson T, Kelly DC, Curtin CM, O'Brien FJ. Mechanosignalling in cartilage: an emerging target for the treatment of osteoarthritis. Nat Rev Rheumatol. 2022; 18: 67‐ 84. 34934171
  131. [137]Dernie F, Adeyoju D. A matter of time: circadian clocks in osteoarthritis and the potential of chronotherapy. Exp Gerontol. 2021; 143: 111163. 33227402
  132. [138]Soul J, Dunn SL, Anand S, et al. Stratification of knee osteoarthritis: two major patient subgroups identified by genome‐wide expression analysis of articular cartilage. Ann Rheum Dis. 2018; 77: 423. 29273645 PMC5867416
  133. [139]Zhu S, Kuek V, Bennett S, Xu H, Rosen V, Xu J. Protein Cytl1: its role in chondrogenesis, cartilage homeostasis, and disease. Cell Mol Life Sci. 2019; 76: 3515‐ 3523. 31089746 PMC6697716
  134. [140]Sanchez C, Mazzucchelli G, Lambert C, Comblain F, DePauw E, Henrotin Y. Comparison of secretome from osteoblasts derived from sclerotic versus non‐sclerotic subchondral bone in OA: a pilot study. PLoS One. 2018; 13: e0194591. 29547667 PMC5856400
  135. [141]Makris EA, Hadidi P, Athanasiou KA. The knee meniscus: structure‐function, pathophysiology, current repair techniques, and prospects for regeneration. Biomaterials. 2011; 32: 7411‐ 7431. 21764438 PMC3161498
  136. [142]Zellner J, Pattappa G, Koch M, et al. Autologous mesenchymal stem cells or meniscal cells: what is the best cell source for regenerative meniscus treatment in an early osteoarthritis situation? Stem Cell Res Ther. 2017; 8: 225. 29017608 PMC5634903
  137. [143]Lee KI, Gamini R, Olmer M, et al. Mohawk is a transcription factor that promotes meniscus cell phenotype and tissue repair and reduces osteoarthritis severity. Sci Transl Med. 2020; 12(567):eaan7967. PMC7955769 33115953
  138. [144]Song H, Guo T, Zhao Z, et al. Biocompatible PEGylated gold nanorods function As cytokinesis inhibitors to suppress angiogenesis. Biomaterials. 2018; 178: 23‐ 35. 29908342
  139. [146]Sun S, Liu H, Hu Y, et al. Selection and identification of a novel ssDNA aptamer targeting human skeletal muscle. Bioact Mater. 2023; 20: 166‐ 178. 35663338 PMC9157180
  140. [147]Yellen BB, Zawistowski JS, Czech EA, et al. Massively parallel quantification of phenotypic heterogeneity in single‐cell drug responses. Sci Adv. 2021; 7: eabf9840. 34533995 PMC8448449
  141. [148]Chen S, Chen X, Geng Z, Su J. The horizon of bone organoid: a perspective on construction and application. Bioact Mater. 2022; 18: 15‐ 25. 35387160 PMC8961298
  142. [149]Kim D, Kobayashi T, Voisin B, et al. Targeted therapy guided by single‐cell transcriptomic analysis in drug‐induced hypersensitivity syndrome: a case report. Nat Med. 2020; 26: 236‐ 243. 31959990 PMC7105105
  143. [152]Castellanos‐Rueda R, Di Roberto RB, Schlatter FS, Reddy ST. Leveraging single‐cell sequencing for chimeric antigen receptor T cell therapies. Trends Biotechnol. 2021; 39: 1308‐ 1320. 33832782
  144. [153]Montoya C, Du Y, Gianforcaro AL, Orrego S, Yang M, Lelkes PI. On the road to smart biomaterials for bone research: definitions, concepts, advances, and outlook. Bone Res. 2021; 9: 12. 33574225 PMC7878740
  145. [154]Sun J, Yin Z, Wang X, Su J. Exosome‐laden hydrogels: a novel cell‐free strategy for In‐situ bone tissue regeneration. Front Bioeng Biotechnol. 2022; 10: 866208. 35433664 PMC9011111
  146. [155]Meng F, Yin Z, Ren X, Geng Z, Su J. Construction of local drug delivery system on titanium‐based implants to improve Osseointegration. Pharmaceutics. 2022; 14(5):1069. PMC9146791 35631656
  147. [156]Wang Z, Li M, Yu B, Cao L, Yang Q, Su J. Nanocalcium‐deficient hydroxyapatite‐poly (e‐caprolactone)‐polyethylene glycol‐poly (e‐caprolactone) composite scaffolds. Int J Nanomedicine. 2012; 7: 3123‐ 3131. 22848159 PMC3405873
  148. [157]Huang J, Fan C, Chen Y, et al. Single‐cell RNA‐seq reveals functionally distinct biomaterial degradation‐related macrophage populations. Biomaterials. 2021; 277: 121116. 34478932
  149. [158]Guo P, Liu X, Zhang P, et al. A single‐cell transcriptome of mesenchymal stromal cells to fabricate bioactive hydroxyapatite materials for bone regeneration. Bioact Mater. 2022; 9: 281‐ 298. 34820571 PMC8586438
  150. [159]Xie C, Liang R, Ye J, et al. High‐efficient engineering of osteo‐callus organoids for rapid bone regeneration within one month. Biomaterials. 2022; 288: 121741. 36031458
  151. [160]Grandi FC, Baskar R, Smeriglio P, et al. Single‐cell mass cytometry reveals cross‐talk between inflammation‐dampening and inflammation‐amplifying cells in osteoarthritic cartilage. Sci Adv. 2020; 6: eaay5352. 32201724 PMC7069698
  152. [161]Shao H, Ge M, Zhang J, Zhao T, Zhang S. Osteoclasts differential‐related prognostic biomarker for osteosarcoma based on single cell, bulk cell and gene expression datasets. BMC Cancer. 2022; 22: 288. 35300639 PMC8932072
  153. [162]Zeng Z, Li W, Zhang D, et al. Development of a Chemoresistant risk scoring model for Prechemotherapy osteosarcoma using single‐cell sequencing. Front Oncol. 2022; 12: 893282. 35664733 PMC9159767
  154. [163]Soul J, Barter MJ, Little CB, Young DA. OATargets: a knowledge base of genes associated with osteoarthritis joint damage in animals. Ann Rheum Dis. 2021; 80: 376‐ 383. 33077471 PMC7892386
  155. [164]Stuart T, Satija R. Integrative single‐cell analysis. Nat Rev Genet. 2019; 20: 257‐ 272. 30696980
  156. [165]Ranzoni AM, Tangherloni A, Berest I, et al. Integrative single‐cell RNA‐Seq and ATAC‐Seq analysis of human developmental hematopoiesis. Cell Stem Cell. 2021; 28: 472‐ 487.e477. 33352111 PMC7939551
  157. [166]Parker E, Hofer IMJ, Rice SJ, et al. Multi‐tissue epigenetic and gene expression analysis combined with epigenome modulation identifies RWDD2B as a target of osteoarthritis susceptibility. Arthritis Rheumatol. 2021; 73: 100‐ 109. 32755071
  158. [167]Rice SJ, Beier F, Young DA, Loughlin J. Interplay between genetics and epigenetics in osteoarthritis. Nat Rev Rheumatol. 2020; 16: 268‐ 281. 32273577
  159. [168]Briggs MT, Kuliwaba JS, Muratovic D, et al. MALDI mass spectrometry imaging of N‐glycans on tibial cartilage and subchondral bone proteins in knee osteoarthritis. Proteomics. 2016; 16: 1736‐ 1741. 26992165
  160. [169]Spitzer MH, Nolan GP. Mass cytometry: single cells, many features. Cell. 2016; 165: 780‐ 791. 27153492 PMC4860251
  161. [170]Othman Z, Cillero Pastor B, van Rijt S, Habibovic P. Understanding interactions between biomaterials and biological systems using proteomics. Biomaterials. 2018; 167: 191‐ 204. 29571054
  162. [171]Liu Y, Yang M, Deng Y, et al. High‐spatial‐resolution multi‐omics sequencing via deterministic barcoding in tissue. Cell. 2020; 183: 1665‐ 1681.e1618. 33188776 PMC7736559
  163. [172]Lei Y, Tang R, Xu J, et al. Applications of single‐cell sequencing in cancer research: progress and perspectives. J Hematol Oncol. 2021; 14: 91. 34108022 PMC8190846
  164. [173]Regner MJ, Wisniewska K, Garcia‐Recio S, et al. A multi‐omic single‐cell landscape of human gynecologic malignancies. Mol Cell. 2021; 81: 4924‐ 4941.e4910. 34739872 PMC8642316
  165. [174]He X, Memczak S, Qu J, Belmonte JCI, Liu GH. Single‐cell omics in ageing: a young and growing field. Nat Metab. 2020; 2: 293‐ 302. 32694606
  166. [175]Lodato MA, Rodin RE, Bohrson CL, et al. Aging and neurodegeneration are associated with increased mutations in single human neurons. Science. 2018; 359: 555‐ 559. 29217584 PMC5831169
  167. [176]Steinberg J, Brooks RA, Southam L, et al. Widespread epigenomic, transcriptomic and proteomic differences between hip osteophytic and articular chondrocytes in osteoarthritis. Rheumatology (Oxford). 2018; 57: 1481‐ 1489. 29741735 PMC6055583
  168. [177]Ratneswaran A, Rockel JS, Kapoor M. Understanding osteoarthritis pathogenesis: a multiomics system‐based approach. Curr Opin Rheumatol. 2020; 32: 80‐ 91. 31724972
  169. [178]Ma A, McDermaid A, Xu J, Chang Y, Ma Q. Integrative methods and practical challenges for single‐cell multi‐omics. Trends Biotechnol. 2020; 38: 1007‐ 1022. 32818441 PMC7442857
  170. [179]Kiselev VY, Andrews TS, Hemberg M. Challenges in unsupervised clustering of single‐cell RNA‐seq data. Nat Rev Genet. 2019; 20: 273‐ 282. 30617341
  171. [180]Rai MF, Wu CL, Capellini TD, et al. Single cell omics for musculoskeletal research. Curr Osteoporos Rep. 2021; 19: 131‐ 140. 33559841 PMC8743139

Cited by

Sorted by citations

Authors
Gu, Y., Hu, Y., Zhang, H., Wang, S., Xu, K., & Su, J.
Affiliations
Shanghai University (CN)
Corresponding author
  • Wang, Sicheng
  • Xu, Ke
  • Su, Jiacan
Venue
Cell Proliferation
Publisher
Wiley
Published
2023-06-14
Volume
56
Issue
12
Pages
e13517-e13517
ISSN
  • 0960-7722 (ISSN-L)
  • 1365-2184
OpenAlex
W4380730812
Cited by
59
References
9
Citations by year
2026: 18 · 2025: 31 · 2024: 9 · 2023: 1
FWCI
2.58
Type
journal article
Language
en
Open access
Locations
  • Cell Proliferation (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China (82172098)
Topics
  • Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone and Joint Diseases
Keywords
osteoarthritis, single-cell RNA sequencing, articular cartilage, meniscus, synovium, subchondral bone, chondrocytes, osteoblasts, fibroblasts, endothelial cells, cell crosstalk, disease heterogeneity, therapeutic target, tissue engineering, personalized medicine, multi-omics
MeSH terms
Bone and Bones, Cartilage, Articular, Humans, Osteoarthritis, Sequence Analysis, RNA, Chondrocytes, Endothelial Cells

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review