Summary: Large HYALURONAN-containing proteoglycans found in articular cartilage (CARTILAGE, ARTICULAR). They form into aggregates that provide tissues with the capacity to resist high compressive and tensile forces.

Top Publications

  1. Perera R, Dissanayake P, Senarath U, Wijayaratne L, Karunanayake A, Dissanayake V. Variants of ACAN are associated with severity of lumbar disc herniation in patients with chronic low back pain. PLoS ONE. 2017;12:e0181580 pubmed publisher
    ..SNVs of ACAN and their haplotypes are associated with the severity of lumbar disc herniation. Functional genetic studies are necessary to identify the role of these significant SNVs in the pathogenesis of disc herniation. ..
  2. Calabro A, Hascall V, Caterson B. Monoclonal antibodies directed against epitopes within the core protein structure of the large aggregating proteoglycan (aggrecan) from the swarm rat chondrosarcoma. Arch Biochem Biophys. 1992;298:349-60 pubmed
    ..These antibodies have been proven to be useful for identifying aggrecan-like molecules in several connective tissues other than cartilage. ..
  3. Juaristi I, Garcia Martin M, Rodrigues T, Satrustegui J, Llorente Folch I, Pardo B. ARALAR/AGC1 deficiency, a neurodevelopmental disorder with severe impairment of neuronal mitochondrial respiration, does not produce a primary increase in brain lactate. J Neurochem. 2017;142:132-139 pubmed publisher
    ..This suggests that glycerol phosphate shuttle is the main NADH shuttle in astrocytes and explains the absence of effects of ARALAR-deficiency in these cells. ..
  4. Zhang Y, Zhao S, Zhu Z, Wang Y, Liu J, Zhang Z, et al. Cx43- and Smad-Mediated TGF-?/ BMP Signaling Pathway Promotes Cartilage Differentiation of Bone Marrow Mesenchymal Stem Cells and Inhibits Osteoblast Differentiation. Cell Physiol Biochem. 2017;42:1277-1293 pubmed publisher
    ..Cx43 and Smad1 promote BMP-induced cartilage differentiation of BMSCs and inhibit osteoblast differentiation, which provide a new strategy for cartilage tissue engineering using exogenous Cx43 and Smad1. ..
  5. Dai L, Zhang X, Hu X, Zhou C, Ao Y. Silencing of microRNA-101 prevents IL-1?-induced extracellular matrix degradation in chondrocytes. Arthritis Res Ther. 2012;14:R268 pubmed publisher
    ..miR-101 participates in IL-1?-induced chondrocyte ECM degradation. Down-regulating miR-101 expression can prevent the IL-1?-induced ECM degradation in chondrocytes. miR-101 probably functions by directly targeting Sox9 mRNA. ..
  6. Buschmann M, Kim Y, Wong M, Frank E, Hunziker E, Grodzinsky A. Stimulation of aggrecan synthesis in cartilage explants by cyclic loading is localized to regions of high interstitial fluid flow. Arch Biochem Biophys. 1999;366:1-7 pubmed
    ..These results reinforce the role of load-induced flow of interstitial fluid in the stimulation of aggrecan production during dynamic loading of cartilage. ..
  7. Lin H, Ma X, Wang B, Zhao L, Liu J, Pu F, et al. Edaravone ameliorates compression-induced damage in rat nucleus pulposus cells. Life Sci. 2017;189:76-83 pubmed publisher
    ..These results strongly indicate that edaravone ameliorates compression-induced damage in rat nucleus pulposus cells. Edaravone could be a potential new drug for treatment of IDD. ..
  8. Nam H, Karunanithi P, Loo W, Naveen S, Chen H, Hussin P, et al. The effects of staged intra-articular injection of cultured autologous mesenchymal stromal cells on the repair of damaged cartilage: a pilot study in caprine model. Arthritis Res Ther. 2013;15:R129 pubmed publisher
    ..Significant differences between these 3 groups were observed (P <0.05). This study suggests that supplementing intra-articular injections of BM-MSCs following BMS knee surgery provides superior cartilage repair outcomes. ..
  9. Young I, Chuang S, Hsu C, Sun Y, Liu H, Chen Y, et al. Protective effects of aucubin on osteoarthritic chondrocyte model induced by hydrogen peroxide and mechanical stimulus. BMC Complement Altern Med. 2017;17:91 pubmed publisher
    ..These results indicated that aucubin has protective effects in an osteoarthritic chondrocyte model induced by H2O2 and mechanical stimulus. ..

More Information


  1. Purmessur D, Guterl C, Cho S, Cornejo M, Lam Y, Ballif B, et al. Dynamic pressurization induces transition of notochordal cells to a mature phenotype while retaining production of important patterning ligands from development. Arthritis Res Ther. 2013;15:R122 pubmed
    ..Bioactive candidates identified from young porcine IVDs may be isolated and harnessed for therapies to target discogenic back pain. ..
  2. Wang Y, Yi X, Li C. Role of thymic stromal lymphopoietin in the pathogenesis of lumbar disc degeneration. Medicine (Baltimore). 2017;96:e7516 pubmed publisher
    ..The evident information obtained from the investigation could lead the way for new therapeutic approaches regarding LDD treatment. ..
  3. Haynesworth S, Carrino D, Caplan A. Characterization of the core protein of the large chondroitin sulfate proteoglycan synthesized by chondrocytes in chick limb bud cell cultures. J Biol Chem. 1987;262:10574-81 pubmed
    ..Based on these observations, a map of the chick chondrocyte proteoglycan core protein has been constructed. ..
  4. Knudson W, Aguiar D, Hua Q, Knudson C. CD44-anchored hyaluronan-rich pericellular matrices: an ultrastructural and biochemical analysis. Exp Cell Res. 1996;228:216-28 pubmed
    ..All of these data suggest that the hyaluronan receptor CD44 retains and participates in the assembly of the chondrocyte pericellular matrix. ..
  5. Taipale M, Solovieva S, Leino Arjas P, Männikkö M. Functional polymorphisms in asporin and CILP together with joint loading predispose to hand osteoarthritis. BMC Genet. 2017;18:108 pubmed publisher
    ..ASPN rs41278695 SNP had an effect on Agc1 and Col2a1 gene expression when induced with BMP-2 suggesting an effect on the cartilage extracellular matrix composition. ..
  6. Liu Z, Li C, Meng X, Bai Y, Qi J, Wang J, et al. Hypoxia-inducible factor-l? mediates aggrecan and collagen ? expression via NOTCH1 signaling in nucleus pulposus cells during intervertebral disc degeneration. Biochem Biophys Res Commun. 2017;488:554-561 pubmed publisher
    ..Therefore, our study shows that HIF-1? regulates collagen ? and aggrecan expression through NOTCH1 signaling and implicate NOTCH1 as a potential therapeutic target in disc degeneration. ..
  7. Paduszyński P, Aleksander Konert E, Zajdel A, Wilczok A, Jelonek K, Witek A, et al. Changes in expression of cartilaginous genes during chondrogenesis of Wharton's jelly mesenchymal stem cells on three-dimensional biodegradable poly(L-lactide-co-glycolide) scaffolds. Cell Mol Biol Lett. 2016;21:14 pubmed publisher
    ..This primary study suggests that chondrogenic capacity of WJ-MSCs cultured on the PLGA scaffolds can be useful for cell therapy of cartilage. ..
  8. Winsz Szczotka K, Komosinska Vassev K, Kuznik Trocha K, Siwiec A, Żegleń B, Olczyk K. Circulating keratan sulfate as a marker of metabolic changes of cartilage proteoglycan in juvenile idiopathic arthritis; influence of growth factors as well as proteolytic and prooxidative agents on aggrecan alterations. Clin Chem Lab Med. 2015;53:291-7 pubmed publisher
  9. Chang Y, Wang X, Sun Z, Jin Z, Chen M, Wang X, et al. Inflammatory cytokine of IL-1? is involved in T-2 toxin-triggered chondrocyte injury and metabolism imbalance by the activation of Wnt/?-catenin signaling. Mol Immunol. 2017;91:195-201 pubmed publisher
    ..Together, this study elucidates a new insight into how T-2 deteriorates the pathological progression of KBD by regulating inflammation-related pathways, indicating a promising anti-inflammation strategy for KBD therapy...
  10. Kintakas C, McCulloch D. Emerging roles for ADAMTS5 during development and disease. Matrix Biol. 2011;30:311-7 pubmed publisher
  11. Srisuthtayanont W, Pruksakorn D, Kongtawelert P, Pothacharoen P. Effects of sesamin on chondroitin sulfate proteoglycan synthesis induced by interleukin-1beta in human chondrocytes. BMC Complement Altern Med. 2017;17:286 pubmed publisher
    ..Sesamin enhances CSPGs synthesis, suppresses IL-1? expression and ameliorates IL-1? induced inflammation in human chondrocytes. Sesamin could have therapeutic benefits for treating inflammation in osteoarthritis. ..
  12. Redeker J, Schmitt B, Grigull N, Braun C, Büttner A, Jansson V, et al. Effect of electromagnetic fields on human osteoarthritic and non-osteoarthritic chondrocytes. BMC Complement Altern Med. 2017;17:402 pubmed publisher
    ..An 8 mT EMF however showed no effect altogether. This suggests that EMF effects are related to EMF but also to chondrocyte quality. Further studies about the clinical relevance of this effect are necessary. ..
  13. Liang W, Li Z, Wang Z, Zhou J, Song H, Xu S, et al. Periodic Mechanical Stress INDUCES Chondrocyte Proliferation and Matrix Synthesis via CaMKII-Mediated Pyk2 Signaling. Cell Physiol Biochem. 2017;42:383-396 pubmed publisher
    ..Our results collectively indicate that periodic mechanical stress promotes chondrocyte proliferation and matrix synthesis through the integrin?1-CaMKII-Pyk2-ERK1/2 signaling cascade. ..
  14. Snow D, Letourneau P. Neurite outgrowth on a step gradient of chondroitin sulfate proteoglycan (CS-PG). J Neurobiol. 1992;23:322-36 pubmed
    ..The different responses of different neuronal types suggest that the presence of sulfated PG may have varying effects on different aspects of neuronal development. ..
  15. Wang K, Li Y, Han R, Cai G, He C, Wang G, et al. T140 blocks the SDF-1/CXCR4 signaling pathway and prevents cartilage degeneration in an osteoarthritis disease model. PLoS ONE. 2017;12:e0176048 pubmed publisher
    ..T140 can downregulate the expression of matrix-degrading enzyme and lessen the degeneration of cartilage by blocking the SDF-1/CRCR4 signaling pathway in vivo. This mechanism may present a pharmacological target for the treatment of OA. ..
  16. Li P, Gan Y, Wang H, Xu Y, Song L, Zhang C, et al. Biological Responses of the Immature Annulus Fibrosus to Dynamic Compression in a Disc Perfusion Culture. Cells Tissues Organs. 2016;202:296-306 pubmed
  17. Gherardini F. Borrelia burgdorferi HtrA may promote dissemination and irritation. Mol Microbiol. 2013;90:209-13 pubmed publisher
  18. Antoniou J, Wang H, Alaseem A, Haglund L, Roughley P, Mwale F. The effect of Link N on differentiation of human bone marrow-derived mesenchymal stem cells. Arthritis Res Ther. 2012;14:R267 pubmed publisher
    ..Link N can enhance chondrogenic differentiation and downregulate hypertrophic and osteogenic differentiation of human MSCs. Therefore, in principle, Link N could be used to optimize MSC-mediated repair of the degenerated disc. ..
  19. Wilkinson D, Habgood A, Lamb H, Thompson P, Hawkins A, Desilets A, et al. Matriptase Induction of Metalloproteinase-Dependent Aggrecanolysis In Vitro and In Vivo: Promotion of Osteoarthritic Cartilage Damage by Multiple Mechanisms. Arthritis Rheumatol. 2017;69:1601-1611 pubmed publisher
    ..Therapeutic targeting of matriptase proteolytic activity reduces metalloproteinase activity, further suggesting that this serine proteinase may have potential as a disease-modifying therapy in OA. ..
  20. Lahm A, Dabravolski D, Spank H, Merk H, Esser J, Kasch R. Regional differences of tibial and femoral cartilage in the chondrocyte gene expression, immunhistochemistry and composite in different stages of osteoarthritis. Tissue Cell. 2017;49:249-256 pubmed publisher
    ..The present study has identified a selection of events which reflect the response of cartilage structure and composite, chondrocytes itself and their productivity to changes in mechanical stress depending on the anatomical site. ..
  21. Fang J, Xiao L, Chen R, Zhao Z. Conditional removal of the canonical TGF-?1 signaling delays condylar cartilage degeneration induced by a partial discectomy in mice. PLoS ONE. 2017;12:e0177826 pubmed publisher
    ..Therefore, inhibition of Tgf-?1 signaling may be able to protect condylar cartilages from being degraded in mature temporomandibular joints. ..
  22. Durham T, Marimuthu J, Toth J, Liu C, Adams L, Mudra D, et al. A Highly Selective Hydantoin Inhibitor of Aggrecanase-1 and Aggrecanase-2 with a Low Projected Human Dose. J Med Chem. 2017;60:5933-5939 pubmed publisher
    ..The projected human dose required to achieve sustained plasma levels ?10 times the hADAMTS-5 IC50 is 5 mg q.d. ..
  23. Catalina Cabrera L, McNabb B, Woods S, Cartoceti A, Busch R. Hydrops associated with chondrodysplasia of the fetus in a miniature Scottish Highland cow. J Am Vet Med Assoc. 2016;248:552-6 pubmed publisher
    ..The findings highlighted the clinical importance of testing for known genetic diseases in breeding cattle, particularly among miniature breeds. ..
  24. Nagai T, Sato M, Kobayashi M, Yokoyama M, Tani Y, Mochida J. Bevacizumab, an anti-vascular endothelial growth factor antibody, inhibits osteoarthritis. Arthritis Res Ther. 2014;16:427 pubmed publisher
    ..Our results suggest that intra-articular bevacizumab may offer a new therapeutic approach for patients with post-traumatic OA. ..
  25. Lee P, Tran K, Chang W, Shelke N, Kumbar S, Yu X. Influence of chondroitin sulfate and hyaluronic acid presence in nanofibers and its alignment on the bone marrow stromal cells: cartilage regeneration. J Biomed Nanotechnol. 2014;10:1469-79 pubmed
    ..This biomimetic and bioactive scaffold may serve as a serve as an efficient scaffold system for cartilage regeneration. ..
  26. Yan J, Yang S, Sun H, Guo D, Wu B, Ji F, et al. Effects of releasing recombinant human growth and differentiation factor-5 from poly(lactic-co-glycolic acid) microspheres for repair of the rat degenerated intervertebral disc. J Biomater Appl. 2014;29:72-80 pubmed publisher
    ..The results of this study suggest that injection of rhGDF-5 loaded in PLGA microspheres into rat tail discs may be as a promising therapy strategy to regenerate or repair the degenerative disc. ..
  27. He J, Zhang J, Wang D. Down-regulation of microRNA-216b inhibits IL-1β-induced chondrocyte injury by up-regulation of Smad3. Biosci Rep. 2017;37: pubmed publisher
    ..Our results suggested that miR-216b contributes to progression of OA by directly targeting Smad3, providing a potential therapeutic target for treatment of OA. ..
  28. Yamamoto K, Santamaria S, Botkjaer K, Dudhia J, Troeberg L, Itoh Y, et al. Inhibition of Shedding of Low-Density Lipoprotein Receptor-Related Protein 1 Reverses Cartilage Matrix Degradation in Osteoarthritis. Arthritis Rheumatol. 2017;69:1246-1256 pubmed publisher
    ..Shedding of LRP-1 is a key link to OA progression. Local inhibition of LRP-1 sheddase activities of ADAM-17 and MMP-14 is a unique way to reverse matrix degradation in OA cartilage and could be effective as a therapeutic approach. ..
  29. Parker E, Vessillier S, Pingguan Murphy B, Abas W, Bader D, Chowdhury T. Low oxygen tension increased fibronectin fragment induced catabolic activities--response prevented with biomechanical signals. Arthritis Res Ther. 2013;15:R163 pubmed publisher
    ..Future investigations will utilize the ex vivo model as a tool to identify key targets and therapeutics for OA treatments. ..