Skip to main content

Advertisement

SpringerLink
Log in

Hyaluronic acid secretion by synoviocytes alters under cyclic compressive load in contracted collagen gels

  • Brief Report
  • Published:
Cytotechnology Aims and scope Submit manuscript

Abstract

Knee osteoarthritis is a degenerative disease of diarthrodial joints. Biomechanical factors are considered as risk factors for the disease, the knee joint being normally subject to pressure. Some studies have examined the biomechanical environment of the knee joint in vitro. The aim of this study was to establish a culture model to mimic the knee joint environment. As a first step, synoviocytes induced contraction of three-dimensional collagen gels. Next, contracted collagen gels containing synoviocytes underwent cyclical compression ranging from 0 to 40 kPa at a frequency of 1.0 Hz for 1.5, 3, 6 and 12 h using the FX-4000C™ Flexercell® Compression Plus™ System. RNA in collagen gels was extracted immediately after compression and mRNA expression levels of HAS genes were analyzed by quantitative RT-PCR. Culture medium was collected 48 h after compression and analyzed by agarose gel electrophoresis and cellulose acetate electrophoresis. Synoviocytes in contracted collagen gels were stimulated by cyclic compressive load. Long-term compressive stimulation led to the production of higher molecular weight hyaluronic acid, whereas, short-term, compressive stimulation increased the total amount of hyaluronic acid. Furthermore, mRNA expression levels of both HAS-1 and HAS-2 were significantly higher than without compression. Taken together, using this gel culture system, synoviocytes synthesized higher molecular weight hyaluronic acid and produced large quantities of hyaluronic acid through up-regulation of HAS gene expression. Therefore, the contracted collagen gel model will be a useful in vitro three-dimensional model of the knee joint.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

References

  • Bell E, Ivarsson B, Merrill C (1979) Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative potential in vitro. Proc Natl Acad Sci USA 76:1274–1278

    Article  CAS  Google Scholar 

  • Bougault C, Paumier A, Aubert-Foucher E, Mallein-Gerin F (2009) Investigating conversion of mechanical force into biochemical signaling in three-dimensional chondrocyte cultures. Nat Protoc 4:928–938

    Article  CAS  Google Scholar 

  • Buschmann MD, Gluzband YA, Grodzinsky AJ, Hunziker EB (1995) Mechanical compression modulates matrix biosynthesis in chondrocyte/agarose culture. J Cell Sci 108:1497–1508

    CAS  Google Scholar 

  • Chevallay B, Herbage D (2000) Collagen-based biomaterials as 3D scaffold for cell cultures: applications for tissue engineering and gene therapy. Med Biol Eng Comput 38:211–218

    Article  CAS  Google Scholar 

  • Coleman PJ, Scott D, Mason RM, Levick JR (2000) Role of hyaluronan chain length in buffering interstitial flow across synovium in rabbits. J Physiol 526:425–434

    Article  CAS  Google Scholar 

  • David-Raoudi M, Deschrevel B, Leclercq S, Galera P, Boumediene K, Pujol JP (2009) Chondroitin sulfate increases hyaluronan production by human synoviocytes through differential regulation of hyaluronan synthases: role of p38 and Akt. Arthritis Rheum 60:760–770. doi:10.1002/art.24302

    Article  CAS  Google Scholar 

  • DeAngelis PL (1999) Molecular directionality of polysaccharide polymerization by the Pasteurella multocida hyaluronan synthase. J Biol Chem 274:26557–26562

    Article  CAS  Google Scholar 

  • Fox DB, Cook JL, Kuroki K, Cockrell M (2006) Effects of dynamic compressive load on collagen-based scaffolds seeded with fibroblast-like synoviocytes. Tissue Eng 12:1527–1537. doi:10.1089/ten.2006.12.1527

    Article  CAS  Google Scholar 

  • Gabay O, Hall DJ, Berenbaum F, Henrotin Y, Sanchez C (2008) Osteoarthritis and obesity: experimental models. Joint Bone Spine 75:675–679

    Article  Google Scholar 

  • Hanthamrongwit M, Reid WH, Grant MH (1996) Chondroitin-6-sulphate incorporated into collagen gels for the growth of human keratinocytes: the effect of cross-linking agents and diamines. Biomaterials 17:775–780

    Article  CAS  Google Scholar 

  • Hata R, Nagai Y (1973) A micro colorimetric determination of acidic glycosaminoglycans by two dimensional electrophoresis on a cellulose acetate strip. Anal Biochem 52:652–656

    Article  CAS  Google Scholar 

  • Knight MM, Lee DA, Bader DL (1998) The influence of elaborated pericellular matrix on the deformation of isolated articular chondrocytes cultured in agarose. Biochim Biophys Acta 1405:67–77

    Article  CAS  Google Scholar 

  • Levick JR, McDonald JN (1989) Ultrastructure of transport pathways in stressed synovium of the knee in anaesthetized rabbits. J Physiol 419:493–508

    Article  CAS  Google Scholar 

  • Lu Y, Levick JR, Wang W (2004) Concentration polarization of hyaluronan on the surface of the synovial lining of infused joints. J Physiol 561:559–573

    Article  CAS  Google Scholar 

  • Martel-Pelletier J, Di Battista JA, Lajeunesse D (1999) Biochemical factors in joint articular tissue degradation in osteoarthritis. In: Reginster JY, Pelletier JP, Martel-Pelletier J, Henrotin Y (eds) Osteoarthritis: clinical and experimental aspects. Springer-Verlag, Berlin, pp 156–187. doi:10.1007/978-3-642-60026-5_9

    Chapter  Google Scholar 

  • Momberger TS, Levick JR, Mason RM (2005) Hyaluronan secretion by synoviocytes is mechanosensitive. Matrix Biol 24:510–519

    Article  CAS  Google Scholar 

  • Momberger TS, Levick JR, Mason RM (2006) Mechanosensitive synoviocytes: a Ca2+-PKCα-MAP kinase pathway contributes to stretch-induced hyaluronan synthesis in vitro. Matrix Biol 25:306–316

    Article  CAS  Google Scholar 

  • Montesano R, Orci L (1988) Transforming growth factor beta stimulates collagen-matrix contraction by fibroblasts: implications for wound healing. Proc Natl Acad Sci USA 85:4894–4897

    Article  CAS  Google Scholar 

  • Nishiyama T, Akutsu N, Horii I, Nakayama Y, Ozawa T, Hayashi T (1991) Response to growth factors of human dermal fibroblasts in a quiescent state owing to cell-matrix contact inhibition. Matrix 11:71–75

    Article  CAS  Google Scholar 

  • Ohara H, Iida H, Ito K, Takeuchi Y, Nomura Y (2010) Effects of Pro-Hyp, a collagen hydrolysate-derived peptide, on hyaluronic acid synthesis using in vitro cultured synovium cells and oral ingestion of collagen hydrolysates in a guinea pig model of osteoarthritis. Biosci Biotechnol Biochem 74:2096–2099

    Article  CAS  Google Scholar 

  • Palmoski M, Brandt K (1976) Hyaluronate-binding by proteoglycans. Comparison of mildly and severely osteoarthritic regions of human femoral cartilage. Clin Chim Acta 70:87–95

    Article  CAS  Google Scholar 

  • Peyron JG, Balazs EA (1974) Preliminary clinical assessment of Na-hyaluronate injection into human arthritic joints. Pathol Biol (Paris) 22:731–736

    CAS  Google Scholar 

  • Rittig M, Flugel C, Prehm P, Lutjen-Drecoll E (1993) Hyaluronan synthase immunoreactivity in the anterior segment of the primate eye. Graefes Arch Clin Exp Ophthalmol 231:313–317

    Article  CAS  Google Scholar 

  • Rizkalla G, Reiner A, Bogoch E, Poole AR (1992) Studies of the articular cartilage proteoglycan aggrecan in health and osteoarthritis. Evidence for molecular heterogeneity and extensive molecular changes in disease. J Clin Invest 90:2268–2277. doi:10.1172/jci116113

    Article  CAS  Google Scholar 

  • Saari H, Konttinen YT, Friman C, Sorsa T (1993) Differential effects of reactive oxygen species on native synovial fluid and purified human umbilical cord hyaluronate. Inflammation 17:403–415

    Article  CAS  Google Scholar 

  • Stone KR, Rodkey WG, Webber R, McKinney L, Steadman JR (1992) Meniscal regeneration with copolymeric collagen scaffolds. In vitro and in vivo studies evaluated clinically, histologically, and biochemically. Am J Sports Med 20:104–111

    Article  CAS  Google Scholar 

  • Stone KR, Steadman JR, Rodkey WG, Li ST (1997) Regeneration of meniscal cartilage with use of a collagen scaffold. Analysis of preliminary data. J Bone Joint Surg Am 79:1770–1777

    CAS  Google Scholar 

  • Takahashi T, Tominaga K, Takano H, Ariyoshi W, Habu M, Fukuda J, Maeda H (2004) A decrease in the molecular weight of hyaluronic acid in synovial fluid from patients with temporomandibular disorders. J Oral Pathol Med 33:224–229

    Article  CAS  Google Scholar 

  • Vernon RB, Gooden MD (2002) An improved method for the collagen gel contraction assay. In Vitro Cell Dev Biol Anim 38:97–101. doi:10.1290/1071-2690(2002)038<0097:aimftc>2.0.co;2

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Applied Protein Chemistry, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, 183-8509, Tokyo, Japan

    Kazuki Uehara, Masao Hara, Toshiki Matsuo, Go Namiki, Mutsuto Watanabe & Yoshihiro Nomura

Authors
  1. Kazuki Uehara
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Masao Hara
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Toshiki Matsuo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Go Namiki
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mutsuto Watanabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yoshihiro Nomura
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yoshihiro Nomura.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Uehara, K., Hara, M., Matsuo, T. et al. Hyaluronic acid secretion by synoviocytes alters under cyclic compressive load in contracted collagen gels. Cytotechnology 67, 19–26 (2015). https://doi.org/10.1007/s10616-013-9669-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10616-013-9669-9

Keywords

Search

Navigation