Reviews

Research progress on matrix⁃chondrocyte interactions in osteoarthritis

  • Guizhi KE ,
  • Yu HUANG ,
  • Liping FU ,
  • Binhua ZOU ,
  • Gang. LIU
Expand
  • Department of Rehabilitation Medicine,Nanfang Hospital,Southern Medical University,Guangzhou 510515,Guangdong,China

Received date: 2025-01-09

  Online published: 2025-05-21

Abstract

The extracellular matrix is an important component of articular cartilage, and in previous studies it was more commonly recognized as a scaffolding structure supporting chondrocytes that provides protection from mechanical loading and elastic compression. As research continues to progress, a large body of literature suggests that the extracellular matrix is dynamic in nature. It degrades, deposits, and releases components in response to changes in its local microenvironment, which in turn dynamically regulates chondrocyte function and fate. Therefore, this review outlines the impact of matrix-chondrocyte interactions on chondrocyte behavior and joint homeostasis in osteoarthritis. It is hoped that the systematic elucidation of matrix-cell reciprocal relationships will provide new insights into the pathological mechanisms of osteoarthritis and the design and construction of cartilage tissue engineering. Specifically, we first summarize the typical molecular components that make up the extracellular matrix and the mechanical properties they confer in the matrix and the mechanotransduction functions they exert in chondrocytes. Next, we discuss the negative impact of chondrocytes on the synthesis and breakdown of matrix components during the osteoarthritic process in response to abnormal mechanical loading in the local microenvironment or disturbance by trauma. Finally, we focus on the impact of an abnormally remodeled extracellular matrix on chondrocyte signaling and the pathological progression of osteoarthritis by mediating the generation of bioactive catabolic fragments, modulating cytokine release, and altering mechanical properties.

Cite this article

Guizhi KE , Yu HUANG , Liping FU , Binhua ZOU , Gang. LIU . Research progress on matrix⁃chondrocyte interactions in osteoarthritis[J]. The Journal of Practical Medicine, 2025 , 41(10) : 1590 -1596 . DOI: 10.3969/j.issn.1006-5725.2025.10.023

References

1 OZEKI N, KOGA H, SEKIYA I. Degenerative Meniscus in Knee Osteoarthritis: From Pathology to Treatment[J]. Life (Basel), 2022, 12(4):603. doi:10.3390/life12040603
2 XIE J, LI S, SONG Z, et al. Functional Monitoring of Patients With Knee Osteoarthritis Based on Multidimensional Wearable Plantar Pressure Features: Cross-Sectional Study[J]. JMIR Aging, 2024, 7:e58261. doi:10.2196/58261
3 WANG F, CAO Y, LU H, et al. Osteoarthritis Incidence Trends Globally, Regionally, and Nationally, 1990-2019: An Age‐Period‐Cohort Analysis[J]. Musculoskeletal Care, 2025, 23(1): e70045. doi:10.1002/msc.70045
4 ZHANG Y, WANG X, CHEN J, et al. Exosomes derived from platelet-rich plasma administration in site mediate cartilage protection in subtalar osteoarthritis[J]. J Nanobiotechnol, 2022, 20(1): 56. doi:10.1186/s12951-022-01245-8
5 EL-SAID K S, ATTA A, MOBASHER M A, et al. Quercetin mitigates rheumatoid arthritis by inhibiting adenosine deaminase in rats[J]. Mol Med, 2022, 28(1): 24. doi:10.1186/s10020-022-00432-5
6 YEO C, AHN C R, KIM J E, et al. Chaenomeles Fructus (CF), the Fruit of Chaenomeles sinensis Alleviates IL-1β Induced Cartilage Degradation in Rat Articular Chondrocytes[J]. Int J Mol Sci, 2022, 23(8): 4360. doi:10.3390/ijms23084360
7 VINCENT T L, WANN A K T. Mechanoadaptation: articular cartilage through thick and thin[J]. J Physiol, 2019, 597(5): 1271-1281. doi:10.1113/jp275451
8 WEI Q, ZHANG X, ZHOU C, et al. Roles of large aggregating proteoglycans in human intervertebral disc degeneration[J]. Connect Tissue Res, 2019, 60(3): 209-218. doi:10.1080/03008207.2018.1499731
9 BROWN S B, HORNYAK J A, JUNGELS R R, et al. Characterization of Post‐Traumatic Osteoarthritis in Rats Following Anterior Cruciate Ligament Rupture by Non‐Invasive Knee Injury (NIKI)[J]. J Orthop Res, 2020, 38(2): 356-367. doi:10.1002/jor.24470
10 CHANALARIS A, CLARKE H, GUIMOND S E, et al. Heparan Sulfate Proteoglycan Synthesis Is Dysregulated in Human Osteoarthritic Cartilage[J]. Am J Pathol, 2019, 189(3): 632-647. doi:10.1016/j.ajpath.2018.11.011
11 LOPEZ S G, BONASSAR L J. The role of SLRPs and large aggregating proteoglycans in collagen fibrillogenesis, extracellular matrix assembly, and mechanical function of fibrocartilage[J]. Connect Tissue Res, 2022, 63(3): 269-286. doi:10.1080/03008207.2021.1903887
12 HAN B, LI Q, WANG C, et al. Differentiated activities of decorin and biglycan in the progression of post-traumatic osteoarthritis[J]. Osteoarthritis Cartilage, 2021, 29(8): 1181-1192. doi:10.1016/j.joca.2021.03.019
13 MELROSE L, FULLER E S, ROUGHLEY P J, et al. Fragmentation of decorin, biglycan, lumican and keratocan is elevated in degenerate human meniscus, knee and hip articular cartilage compared with age?matched macroscopically hormal and control tissues[J]. Arthritis Res Ther, 2008,10(4):R79. doi:10.1186/ar2453
14 SALMINEN A. Increased immunosuppression impairs tissue homeostasis with aging and age-related diseases[J]. J Mol Med (Berl), 2021, 99(1): 1-20. doi:10.1007/s00109-020-01988-7
15 MONACO G, QAWASMI F, EL HAJ A J, et al. Chondrogenic differentiation of human bone marrow MSCs in osteochondral implants under kinematic mechanical load is dependent on the underlying osteo component[J]. Front Bioeng Biotechnol, 2022, 10: 998774. doi:10.3389/fbioe.2022.998774
16 TSENG H C, WU M R, LEE C H, et al. Differentiation Capacity of Bone Marrow-Derived Rat Mesenchymal Stem Cells from DsRed and Cre Transgenic Cre/loxP Models[J]. Cells, 2022, 11(17): 2769. doi:10.3390/cells11172769
17 CHEN L, WEI K, LI J, et al. Integrated Analysis of LncRNA-Mediated ceRNA Network in Calcific Aortic Valve Disease[J]. Cells, 2022, 11(14): 2204. doi:10.3390/cells11142204
18 ARMIENTO A R, ALINI M, STODDART M J. Articular fibrocartilage-Why does hyaline cartilage fail to repair?[J]. Adv Drug Deliv Rev, 2019, 146: 289-305. doi:10.1016/j.addr.2018.12.015
19 GAN K, LIAN H, YANG T, et al. Periplogenin attenuates LPS-mediated inflammatory osteolysis through the suppression of osteoclastogenesis via reducing the NF-κB and MAPK signaling pathways[J]. Cell Death Discovery, 2024, 10(1): 86. doi:10.1038/s41420-024-01856-0
20 EVERS B J, VAN DEN BOSCH M H J, BLOM A B, et al. Post-traumatic knee osteoarthritis; the role of inflammation and hemarthrosis on disease progression[J]. Front Med (Lausanne), 2022, 9: 973870. doi:10.3389/fmed.2022.973870
21 AVENOSO A, D′ASCOLA A, SCURUCHI M, et al. Hyaluronan in the experimental injury of the cartilage: biochemical action and protective effects[J]. Inflamm Res, 2018, 67(1): 5-20. doi:10.1007/s00011-017-1084-9
22 SUZUKI M, TAKAHASHI N, SOBUE Y, et al. Hyaluronan suppresses enhanced cathepsin K expression via activation of NF-κB with mechanical stress loading in a human chondrocytic HCS-2/8 cells[J]. Sci Rep, 2020, 10(1): 216. doi:10.1038/s41598-019-57073-8
23 ROEDIG H, NASTASE M V, WYGRECKA M, et al. Breaking down chronic inflammatory diseases: The role of biglycan in promoting a switch between inflammation and autophagy[J]. FEBS J, 2019, 286(15): 2965-2979. doi:10.1111/febs.14791
24 AVENOSO A, D’ASCOLA A, SCURUCHI M, et al. The proteoglycan biglycan mediates inflammatory response by activating TLR-4 in human chondrocytes: Inhibition by specific siRNA and high polymerized Hyaluronan[J]. Arch Biochem Biophys, 2018, 640: 75-82. doi:10.1016/j.abb.2018.01.007
25 ZHAO F, BAI Y, XIANG X, et al. The role of fibromodulin in inflammatory responses and diseases associated with inflammation[J]. Front Immunol, 2023, 14: 1191787. doi:10.3389/fimmu.2023.1191787
26 LAMBERT C, ZAPPIA J, SANCHEZ C, et al. The Damage-Associated Molecular Patterns (DAMPs) as Potential Targets to Treat Osteoarthritis: Perspectives From a Review of the Literature[J]. Front Med (Lausanne), 2021, 7: 607186. doi:10.3389/fmed.2020.607186
27 WANG Y, LI L, WEI Q, et al. Design, Preparation, and Bioactivity Study of New Fusion Protein HB-NC4 in the Treatment of Osteoarthritis[J]. Front Bioeng Biotechnol, 2021, 9: 700064. doi:10.3389/fbioe.2021.700064
28 AHANGAR P, MILLS S J, COWIN A J. Mesenchymal Stem Cell Secretome as an Emerging Cell-Free Alternative for Improving Wound Repair[J]. Int J Mol Sci, 2020, 21(19): 7038. doi:10.3390/ijms21197038
29 WU M, WU S, CHEN W, et al. The roles and regulatory mechanisms of TGF-β and BMP signaling in bone and cartilage development, homeostasis and disease[J]. Cell Res, 2024, 34(2): 101-123. doi:10.1038/s41422-023-00918-9
30 ORNITZ D M, MARIE P J. Fibroblast growth factors in skeletal development[J]. Curr Top Dev Biol, 2019, 133: 195-234. doi:10.1016/bs.ctdb.2018.11.020
31 WANG X, LU Y, WANG W, et al. Effect of different aged cartilage ECM on chondrogenesis of BMSCs in vitro and in vivo[J]. Regen Biomater, 2020, 7(6): 583-595. doi:10.1093/rb/rbaa028
32 ZHANG W, LIN Z, SHI F, et al. HSPG2 Mutation Association with Immune Checkpoint Inhibitor Outcome in Melanoma and Non-Small Cell Lung Cancer[J]. Cancers, 2022, 14(14): 3495. doi:10.3390/cancers14143495
33 LI L, MENG L, XU C Q, et al. Effect of cell receptors in the pathogenesis of osteoarthritis: Current insights[J]. Open Life Sci, 2022, 17(1): 695-709. doi:10.1515/biol-2022-0075
34 KONG K, LI B, CHANG Y, et al. Delivery of FGF18 using mRNA-LNP protects the cartilage against degeneration via alleviating chondrocyte senescence[J]. Nanobiotechnol, 2025, 23(1): 34. doi:10.1186/s12951-025-03103-9
35 XIANG P, LUO Z P, CHE Y J. Insights into the mechanical microenvironment within the cartilaginous endplate: An emerging role in maintaining disc homeostasis and normal function[J]. Heliyon, 2024, 10(10): e31162. doi:10.1016/j.heliyon.2024.e31162
36 CHEN J, WANG N. Tissue cell differentiation and multicellular evolution via cytoskeletal stiffening in mechanically stressed microenvironments[J]. Acta Mech Sin, 2019, 35(2): 270-274. doi:10.1007/s10409-018-0814-8
37 LEWIS W, PADILLA-MARTINEZ J P, ORTEGA-MARTINEZ A, et al. Changes in endogenous UV fluorescence and biomechanical stiffness of bovine articular cartilage after collagenase digestion are strongly correlated[J]. J Biophotonics, 2017, 10(8): 1018-1025. doi:10.1002/jbio.201600093
38 WANG S L, LIU X L, KANG Z C, et al. Platelet-rich plasma promotes peripheral nerve regeneration after sciatic nerve injury[J]. Neural Regen Res, 2023, 18(2): 375. doi:10.4103/1673-5374.346461
39 HUANG H, TAN Y, AYERS D C, et al. Anionic and Zwitterionic Residues Modulate Stiffness of Photo-Cross-Linked Hydrogels and Cellular Behavior of Encapsulated Chondrocytes[J]. ACS Biomater Sci Eng, 2018, 4(5):1843-1851.
40 TAN S, FANG W, VANGSNESS C T, et al. Influence of Cellular Microenvironment on Human Articular Chondrocyte Cell Signaling[J]. Cartilage, 2021, 13(): 935S-946S. doi:10.1177/1947603520941219
41 FU B, SHEN J, ZOU X, et al. Matrix stiffening promotes chondrocyte senescence and the osteoarthritis development through downregulating HDAC3[J]. Bone Res, 2024, 12(1): 32. doi:10.1038/s41413-024-00333-9
42 WU D T, JEFFREYS N, DIBA M, et al. Viscoelastic biomaterials for tissue regeneration[J]. Tissue Eng Part C Methods, 2022, 28(7): 289-300. doi:10.1089/ten.tec.2022.0040
43 RICHARDSON B M, WALKER C J, MAPLES M M, et al. Mechanobiological Interactions between Dynamic Compressive Loading and Viscoelasticity on Chondrocytes in Hydrazone Covalent Adaptable Networks for Cartilage Tissue Engineering[J]. Adv Healthcare Materials, 2021, 10(9): 2002030. doi:10.1002/adhm.202002030
44 LIU D, ZHANG H, DONG X, et al. Effect of viscoelastic properties of cellulose nanocrystal/collagen hydrogels on chondrocyte behaviors[J]. Front Bioeng Biotechnol, 2022, 10: 959409. doi:10.3389/fbioe.2022.959409
45 AGARWAL P, LEE H P, SMERIGLIO P, et al. A dysfunctional TRPV4-GSK3β pathway prevents osteoarthritic chondrocytes from sensing changes in extracellular matrix viscoelasticity[J]. Nat Biomed Eng, 2021, 5(12): 1472-1484. doi:10.1038/s41551-021-00691-3
46 NüRNBERGER S, SCHNEIDER C, KEIBL C, et al. Repopulation of decellularised articular cartilage by laser-based matrix engraving[J]. EBioMedicine, 2021, 64: 103196. doi:10.1016/j.ebiom.2020.103196
47 WANG Z, HAN L, SUN T, et al. Extracellular matrix derived from allogenic decellularized bone marrow mesenchymal stem cell sheets for the reconstruction of osteochondral defects in rabbits[J]. Acta Biomater, 2020, 118: 54-68. doi:10.1016/j.actbio.2020.10.022
48 JIANG S, TIAN G, YANG Z, et al. Enhancement of acellular cartilage matrix scaffold by wharton′s jelly mesenchymal stem cell-derived exosomes to promote osteochondral regeneration[J]. Bioact Mater, 2021, 6(9): 2711-2728. doi:10.1016/j.bioactmat.2021.01.031
49 TANG Q, LIM T, SHEN L Y, et al. Well-dispersed platelet lysate entrapped nanoparticles incorporate with injectable PDLLA-PEG-PDLLA triblock for preferable cartilage engineering application[J]. Biomaterials, 2021, 268: 120605. doi:10.1016/j.biomaterials.2020.120605
50 SESSA A, ROMANDINI I, ANDRIOLO L, et al. Treatment of Juvenile Knee Osteochondritis Dissecans with a Cell-Free Biomimetic Osteochondral Scaffold: Clinical and MRI Results at Mid-Term Follow-up[J]. Cartilage, 2021, 13(): 1137S-1147S. doi:10.1177/1947603520954500
51 COLE B J, HAUNSCHILD E D, CARTER T, et al. Clinically significant outcomes following the treatment of focal cartilage defects of the knee with microfracture augmentation using cartilage allograft extracellular matrix: A multicenter prospective study[J].J Arthrosc Relat Surg, 2021, 37(5): 1512-1521. doi:10.1016/j.arthro.2021.01.043
Outlines

/