Skip to main content
SpringerLink
Log in

Growth Factors in Cartilage Repair

  • Chapter
  • First Online:
Cartilage

Abstract

The articular cartilage does not heal completely after injury, predisposing patients to accelerated progression of degenerative joint disease. While surgical intervention can address chondral defects and yield positive functional outcomes, substantial research has gone into the use of growth factors to augment cartilage repair and preclude or postpone the need for operative management. This chapter describes the growth factors with the most promising in vitro and in vivo data in cartilage repair, namely, bone morphogenetic protein-7, transforming growth factor-β, fibroblast growth factor-18, connective tissue growth factor, insulin-like growth factor-1, and recent advancements with autologous solutions of growth factors, such as platelet-rich plasma. Each section provides a background on mechanism of action, summarizes pivotal basic science research, and describes the results of clinical application in animal and human models of chondral disease.

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

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 179.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  • Abe T, Yamada H, Nakajima H, Kikuchi T, Takaishi H, Tadakuma T, Fujikawa K, Toyama Y (2003) Repair of full-thickness cartilage defects using liposomal transforming growth factor-beta1. J Orthop Sci 8(1):92–101. doi:10.1007/s007760300016

    Article  CAS  PubMed  Google Scholar 

  • Akeda K, An HS, Okuma M, Attawia M, Miyamoto K, Thonar EJ, Lenz ME, Sah RL, Masuda K (2006) Platelet-rich plasma stimulates porcine articular chondrocyte proliferation and matrix biosynthesis. Osteoarthritis Cartilage 14(12):1272–1280. doi:10.1016/j.joca.2006.05.008

    Article  CAS  PubMed  Google Scholar 

  • Badlani N, Oshima Y, Healey R, Coutts R, Amiel D (2009) Use of bone morphogenetic protein-7 as a treatment for osteoarthritis. Clin Orthop Relat Res 467(12):3221–3229. doi:10.1007/s11999-008-0569-9

    Article  PubMed  Google Scholar 

  • Barr L, Getgood A, Guehring H, Rushton N, Henson FM (2014) The effect of recombinant human fibroblast growth factor-18 on articular cartilage following single impact load. J Orthop Res 32(7):923–927. doi:10.1002/jor.22622

    Article  CAS  PubMed  Google Scholar 

  • Blaney Davidson EN, van der Kraan PM, van den Berg WB (2007) TGF-beta and osteoarthritis. Osteoarthritis Cartilage 15(6):597–604. doi:10.1016/j.joca.2007.02.005

    Article  CAS  PubMed  Google Scholar 

  • Bradley EW, Carpio LR, Newton AC, Westendorf JJ (2015) Deletion of the PH-domain and Leucine-rich repeat protein phosphatase 1 (Phlpp1) increases fibroblast growth factor (Fgf) 18 expression and promotes chondrocyte proliferation. J Biol Chem 290(26):16272–16280. doi:10.1074/jbc.M114.612937

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Campbell KA, Saltzman BM, Mascarenhas R, Khair MM, Verma NN, Bach BR Jr, Cole BJ (2015) Does intra-articular platelet-rich plasma injection provide clinically superior outcomes compared with other therapies in the treatment of knee Osteoarthritis? A systematic review of overlapping meta-analyses. Arthroscopy. doi:10.1016/j.arthro.2015.03.041

    Google Scholar 

  • Cerza F, Carni S, Carcangiu A, Di Vavo I, Schiavilla V, Pecora A, De Biasi G, Ciuffreda M (2012) Comparison between hyaluronic acid and platelet-rich plasma, intra-articular infiltration in the treatment of gonarthrosis. Am J Sports Med 40(12):2822–2827. doi:10.1177/0363546512461902

    Article  PubMed  Google Scholar 

  • Cherian JJ, Parvizi J, Bramlet D, Lee KH, Romness DW, Mont MA (2015) Preliminary results of a phase II randomized study to determine the efficacy and safety of genetically engineered allogeneic human chondrocytes expressing TGF-beta1 in patients with grade 3 chronic degenerative joint disease of the knee. Osteoarthritis Cartilage 23(12):2109–2118. doi:10.1016/j.joca.2015.06.019

    Article  CAS  PubMed  Google Scholar 

  • Chubinskaya S, Hakimiyan A, Pacione C, Yanke A, Rappoport L, Aigner T, Rueger DC, Loeser RF (2007a) Synergistic effect of IGF-1 and OP-1 on matrix formation by normal and OA chondrocytes cultured in alginate beads. Osteoarthritis Cartilage 15(4):421–430. doi:10.1016/j.joca.2006.10.004

    Article  CAS  PubMed  Google Scholar 

  • Chubinskaya S, Hurtig M, Rueger DC (2007b) OP-1/BMP-7 in cartilage repair. Int Orthop 31(6):773–781. doi:10.1007/s00264-007-0423-9

    Article  PubMed  PubMed Central  Google Scholar 

  • Chubinskaya S, Segalite D, Pikovsky D, Hakimiyan AA, Rueger DC (2008) Effects induced by BMPS in cultures of human articular chondrocytes: comparative studies. Growth Factors 26(5):275–283. doi:10.1080/08977190802291733

    Article  CAS  PubMed  Google Scholar 

  • Chubinskaya S, Otten L, Soeder S, Borgia JA, Aigner T, Rueger DC, Loeser RF (2011) Regulation of chondrocyte gene expression by osteogenic protein-1. Arthritis Res Ther 13(2):R55. doi:10.1186/ar3300

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Diao H, Wang J, Shen C, Xia S, Guo T, Dong L, Zhang C, Chen J, Zhao J, Zhang J (2009) Improved cartilage regeneration utilizing mesenchymal stem cells in TGF-beta1 gene-activated scaffolds. Tissue Eng Part A 15(9):2687–2698. doi:10.1089/ten.TEA.2008.0621

    Article  CAS  PubMed  Google Scholar 

  • Ekenstedt KJ, Sonntag WE, Loeser RF, Lindgren BR, Carlson CS (2006) Effects of chronic growth hormone and insulin-like growth factor 1 deficiency on osteoarthritis severity in rat knee joints. Arthritis Rheum 54(12):3850–3858. doi:10.1002/art.22254

    Article  CAS  PubMed  Google Scholar 

  • Ellman MB, An HS, Muddasani P, Im HJ (2008) Biological impact of the fibroblast growth factor family on articular cartilage and intervertebral disc homeostasis. Gene 420(1):82–89. doi:10.1016/j.gene.2008.04.019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ellman MB, Yan D, Ahmadinia K, Chen D, An HS, Im HJ (2013) Fibroblast growth factor control of cartilage homeostasis. J Cell Biochem 114(4):735–742. doi:10.1002/jcb.24418

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ellsworth JL, Berry J, Bukowski T, Claus J, Feldhaus A, Holderman S, Holdren MS, Lum KD, Moore EE, Raymond F, Ren H, Shea P, Sprecher C, Storey H, Thompson DL, Waggie K, Yao L, Fernandes RJ, Eyre DR, Hughes SD (2002) Fibroblast growth factor-18 is a trophic factor for mature chondrocytes and their progenitors. Osteoarthritis Cartilage 10(4):308–320. doi:10.1053/joca.2002.0514

    Article  CAS  PubMed  Google Scholar 

  • Elshaier AM, Hakimiyan AA, Rappoport L, Rueger DC, Chubinskaya S (2009) Effect of interleukin-1beta on osteogenic protein 1-induced signaling in adult human articular chondrocytes. Arthritis Rheum 60(1):143–154. doi:10.1002/art.24151

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fan J, Gong Y, Ren L, Varshney RR, Cai D, Wang DA (2010) In vitro engineered cartilage using synovium-derived mesenchymal stem cells with injectable gellan hydrogels. Acta Biomater 6(3):1178–1185. doi:10.1016/j.actbio.2009.08.042

    Article  CAS  PubMed  Google Scholar 

  • Felson DT, Naimark A, Anderson J, Kazis L, Castelli W, Meenan RF (1987) The prevalence of knee osteoarthritis in the elderly. The Framingham Osteoarthritis Study. Arthritis Rheum 30(8):914–918

    Article  CAS  PubMed  Google Scholar 

  • Filardo G, Kon E, Di Martino A, Di Matteo B, Merli ML, Cenacchi A, Fornasari PM, Marcacci M (2012) Platelet-rich plasma vs hyaluronic acid to treat knee degenerative pathology: study design and preliminary results of a randomized controlled trial. BMC Musculoskelet Disord 13:229. doi:10.1186/1471-2474-13-229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Filardo G, Di Matteo B, Di Martino A, Merli ML, Cenacchi A, Fornasari P, Marcacci M, Kon E (2015) Platelet-rich plasma intra-articular knee injections show no superiority versus viscosupplementation: a randomized controlled trial. Am J Sports Med 43(7):1575–1582. doi:10.1177/0363546515582027

    Article  PubMed  Google Scholar 

  • Fortier LA, Mohammed HO, Lust G, Nixon AJ (2002) Insulin-like growth factor-I enhances cell-based repair of articular cartilage. J Bone Joint Surg Br 84(2):276–288

    Article  CAS  PubMed  Google Scholar 

  • Fortier LA, Barker JU, Strauss EJ, McCarrel TM, Cole BJ (2011) The role of growth factors in cartilage repair. Clin Orthop Relat Res 469(10):2706–2715. doi:10.1007/s11999-011-1857-3

    Article  PubMed  PubMed Central  Google Scholar 

  • Friedl A, Chang Z, Tierney A, Rapraeger AC (1997) Differential binding of fibroblast growth factor-2 and -7 to basement membrane heparan sulfate: comparison of normal and abnormal human tissues. Am J Pathol 150(4):1443–1455

    CAS  PubMed  PubMed Central  Google Scholar 

  • Giannoudis PV, Einhorn TA, Schmidmaier G, Marsh D (2008) The diamond concept--open questions. Injury 39(Suppl 2):S5–S8. doi:10.1016/s0020-1383(08)70010-x

    Article  PubMed  Google Scholar 

  • Gobbi A, Karnatzikos G, Mahajan V, Malchira S (2012) Platelet-rich plasma treatment in symptomatic patients with knee osteoarthritis: preliminary results in a group of active patients. Sports Health 4(2):162–172. doi:10.1177/1941738111431801

    Article  PubMed  PubMed Central  Google Scholar 

  • Goldring MB, Tsuchimochi K, Ijiri K (2006) The control of chondrogenesis. J Cell Biochem 97(1):33–44. doi:10.1002/jcb.20652

    Article  CAS  PubMed  Google Scholar 

  • Goodrich LR, Hidaka C, Robbins PD, Evans CH, Nixon AJ (2007) Genetic modification of chondrocytes with insulin-like growth factor-1 enhances cartilage healing in an equine model. J Bone Joint Surg Br 89(5):672–685. doi:10.1302/0301-620x.89b5.18343

    Article  CAS  PubMed  Google Scholar 

  • Goumans MJ, Mummery C (2000) Functional analysis of the TGFbeta receptor/Smad pathway through gene ablation in mice. Int J Dev Biol 44(3):253–265

    CAS  PubMed  Google Scholar 

  • Grgic M, Jelic M, Basic V, Basic N, Pecina M, Vukicevic S (1997) Regeneration of articular cartilage defects in rabbits by osteogenic protein-1 (bone morphogenetic protein-7). Acta Med Croatica 51(1):23–27

    CAS  PubMed  Google Scholar 

  • Ha CW, Noh MJ, Choi KB, Lee KH (2012) Initial phase I safety of retrovirally transduced human chondrocytes expressing transforming growth factor-beta-1 in degenerative arthritis patients. Cytotherapy 14(2):247–256. doi:10.3109/14653249.2011.629645

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hayashi M, Muneta T, Ju YJ, Mochizuki T, Sekiya I (2008) Weekly intra-articular injections of bone morphogenetic protein-7 inhibits osteoarthritis progression. Arthritis Res Ther 10(5):R118. doi:10.1186/ar2521

    Article  PubMed  PubMed Central  Google Scholar 

  • Henson FM, Bowe EA, Davies ME (2005) Promotion of the intrinsic damage-repair response in articular cartilage by fibroblastic growth factor-2. Osteoarthritis Cartilage 13(6):537–544. doi:10.1016/j.joca.2005.02.007

    Article  CAS  PubMed  Google Scholar 

  • Hunter DJ, Pike MC, Jonas BL, Kissin E, Krop J, McAlindon T (2010) Phase 1 safety and tolerability study of BMP-7 in symptomatic knee osteoarthritis. BMC Musculoskelet Disord 11:232. doi:10.1186/1471-2474-11-232

    Article  PubMed  PubMed Central  Google Scholar 

  • Hurtig M, Chubinskaya S, Dickey J, Rueger D (2009) BMP-7 protects against progression of cartilage degeneration after impact injury. J Orthop Res 27(5):602–611. doi:10.1002/jor.20787

    Article  CAS  PubMed  Google Scholar 

  • Im HJ, Pacione C, Chubinskaya S, Van Wijnen AJ, Sun Y, Loeser RF (2003) Inhibitory effects of insulin-like growth factor-1 and osteogenic protein-1 on fibronectin fragment- and interleukin-1beta-stimulated matrix metalloproteinase-13 expression in human chondrocytes. J Biol Chem 278(28):25386–25394. doi:10.1074/jbc.M302048200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Im HJ, Li X, Muddasani P, Kim GH, Davis F, Rangan J, Forsyth CB, Ellman M, Thonar EJ (2008) Basic fibroblast growth factor accelerates matrix degradation via a neuro-endocrine pathway in human adult articular chondrocytes. J Cell Physiol 215(2):452–463. doi:10.1002/jcp.21317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Itoh S, Itoh F, Goumans MJ, Ten Dijke P (2000) Signaling of transforming growth factor-beta family members through Smad proteins. Eur J Biochem 267(24):6954–6967

    Article  CAS  PubMed  Google Scholar 

  • Itoh S, Hattori T, Tomita N, Aoyama E, Yutani Y, Yamashiro T, Takigawa M (2013) CCN family member 2/connective tissue growth factor (CCN2/CTGF) has anti-aging effects that protect articular cartilage from age-related degenerative changes. PLoS One 8(8):e71156. doi:10.1371/journal.pone.0071156

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ivkovic S, Yoon BS, Popoff SN, Safadi FF, Libuda DE, Stephenson RC, Daluiski A, Lyons KM (2003) Connective tissue growth factor coordinates chondrogenesis and angiogenesis during skeletal development. Development 130(12):2779–2791

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jelic M, Pecina M, Haspl M, Kos J, Taylor K, Maticic D, McCartney J, Yin S, Rueger D, Vukicevic S (2001) Regeneration of articular cartilage chondral defects by osteogenic protein-1 (bone morphogenetic protein-7) in sheep. Growth Factors 19(2):101–113

    Article  CAS  PubMed  Google Scholar 

  • Jordan JM, Helmick CG, Renner JB, Luta G, Dragomir AD, Woodard J, Fang F, Schwartz TA, Abbate LM, Callahan LF, Kalsbeek WD, Hochberg MC (2007) Prevalence of knee symptoms and radiographic and symptomatic knee osteoarthritis in African Americans and Caucasians: the Johnston County Osteoarthritis Project. J Rheumatol 34(1):172–180

    PubMed  Google Scholar 

  • Kawaki H, Kubota S, Suzuki A, Lazar N, Yamada T, Matsumura T, Ohgawara T, Maeda T, Perbal B, Lyons KM, Takigawa M (2008) Cooperative regulation of chondrocyte differentiation by CCN2 and CCN3 shown by a comprehensive analysis of the CCN family proteins in cartilage. J Bone Miner Res 23(11):1751–1764. doi:10.1359/jbmr.080615

    Article  CAS  PubMed  Google Scholar 

  • Kon E, Buda R, Filardo G, Di Martino A, Timoncini A, Cenacchi A, Fornasari PM, Giannini S, Marcacci M (2010) Platelet-rich plasma: intra-articular knee injections produced favorable results on degenerative cartilage lesions. Knee Surg Sports Traumatol Arthrosc 18(4):472–479. doi:10.1007/s00167-009-0940-8

    Article  PubMed  Google Scholar 

  • Kern D, Zlatkin MB, Dalinka MK (1988) Occupational and post-traumatic arthritis. Radiol Clin North Am 26(6):1349–1358

    Google Scholar 

  • Kuo AC, Rodrigo JJ, Reddi AH, Curtiss S, Grotkopp E, Chiu M (2006) Microfracture and bone morphogenetic protein 7 (BMP-7) synergistically stimulate articular cartilage repair. Osteoarthritis Cartilage 14(11):1126–1135. doi:10.1016/j.joca.2006.04.004

    Article  CAS  PubMed  Google Scholar 

  • Kurth T, Hedbom E, Shintani N, Sugimoto M, Chen FH, Haspl M, Martinovic S, Hunziker EB (2007) Chondrogenic potential of human synovial mesenchymal stem cells in alginate. Osteoarthritis Cartilage 15(10):1178–1189. doi:10.1016/j.joca.2007.03.015

    Article  CAS  PubMed  Google Scholar 

  • Lee KH, Song SU, Hwang TS, Yi Y, Oh IS, Lee JY, Choi KB, Choi MS, Kim SJ (2001) Regeneration of hyaline cartilage by cell-mediated gene therapy using transforming growth factor beta 1-producing fibroblasts. Hum Gene Ther 12(14):1805–1813. doi:10.1089/104303401750476294

    Article  CAS  PubMed  Google Scholar 

  • Lee MC, Ha CW, Elmallah RK, Cherian JJ, Cho JJ, Kim TW, Bin SI, Mont MA (2015) A placebo-controlled randomised trial to assess the effect of TGF-ss1-expressing chondrocytes in patients with arthritis of the knee. Bone Joint J 97-B(7):924–932. doi:10.1302/0301-620x.97b7.35852

  • Lires-Dean M, Carames B, Cillero-Pastor B, Galdo F, Lopez-Armada MJ, Blanco FJ (2008) Anti-apoptotic effect of transforming growth factor-beta1 on human articular chondrocytes: role of protein phosphatase 2A. Osteoarthritis Cartilage 16(11):1370–1378. doi:10.1016/j.joca.2008.04.001

    Article  CAS  PubMed  Google Scholar 

  • Liu Z, Xu J, Colvin JS, Ornitz DM (2002) Coordination of chondrogenesis and osteogenesis by fibroblast growth factor 18. Genes Dev 16(7):859–869. doi:10.1101/gad.965602

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu Z, Lavine KJ, Hung IH, Ornitz DM (2007) FGF18 is required for early chondrocyte proliferation, hypertrophy and vascular invasion of the growth plate. Dev Biol 302(1):80–91. doi:10.1016/j.ydbio.2006.08.071

    Article  CAS  PubMed  Google Scholar 

  • Loeser RF, Shanker G, Carlson CS, Gardin JF, Shelton BJ, Sonntag WE (2000) Reduction in the chondrocyte response to insulin-like growth factor 1 in aging and osteoarthritis: studies in a non-human primate model of naturally occurring disease. Arthritis Rheum 43(9):2110–2120. doi:10.1002/1529-0131(200009)43:9<2110::aid-anr23>3.0.co;2-u

    Article  CAS  PubMed  Google Scholar 

  • Loeser RF, Carlson CS, Del Carlo M, Cole A (2002) Detection of nitrotyrosine in aging and osteoarthritic cartilage: correlation of oxidative damage with the presence of interleukin-1beta and with chondrocyte resistance to insulin-like growth factor 1. Arthritis Rheum 46(9):2349–2357. doi:10.1002/art.10496

    Article  CAS  PubMed  Google Scholar 

  • Loeser RF, Pacione CA, Chubinskaya S (2003) The combination of insulin-like growth factor 1 and osteogenic protein 1 promotes increased survival of and matrix synthesis by normal and osteoarthritic human articular chondrocytes. Arthritis Rheum 48(8):2188–2196. doi:10.1002/art.11209

    Article  CAS  PubMed  Google Scholar 

  • Loeser RF, Chubinskaya S, Pacione C, Im HJ (2005) Basic fibroblast growth factor inhibits the anabolic activity of insulin-like growth factor 1 and osteogenic protein 1 in adult human articular chondrocytes. Arthritis Rheum 52(12):3910–3917. doi:10.1002/art.21472

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Loeser RF, Gandhi U, Long DL, Yin W, Chubinskaya S (2014) Aging and oxidative stress reduce the response of human articular chondrocytes to insulin-like growth factor 1 and osteogenic protein 1. Arthritis Rheumatol 66(8):2201–2209. doi:10.1002/art.38641

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lohmander LS, Hellot S, Dreher D, Krantz EF, Kruger DS, Guermazi A, Eckstein F (2014) Intraarticular sprifermin (recombinant human fibroblast growth factor 18) in knee osteoarthritis: a randomized, double-blind, placebo-controlled trial. Arthritis Rheumatol 66(7):1820–1831. doi:10.1002/art.38614

    Article  CAS  PubMed  Google Scholar 

  • Lotz M, Rosen F, McCabe G, Quach J, Blanco F, Dudler J, Solan J, Goding J, Seegmiller JE, Terkeltaub R (1995) Interleukin 1 beta suppresses transforming growth factor-induced inorganic pyrophosphate (PPi) production and expression of the PPi-generating enzyme PC-1 in human chondrocytes. Proc Natl Acad Sci U S A 92(22):10364–10368

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mason JM, Breitbart AS, Barcia M, Porti D, Pergolizzi RG, Grande DA (2000) Cartilage and bone regeneration using gene-enhanced tissue engineering. Clin Orthop Relat Res (379 Suppl):S171–S178

    Google Scholar 

  • Massague J, Chen YG (2000) Controlling TGF-beta signaling. Genes Dev 14(6):627–644

    CAS  PubMed  Google Scholar 

  • Mei-Dan O, Carmont MR, Laver L, Mann G, Maffulli N, Nyska M (2012) Platelet-rich plasma or hyaluronate in the management of osteochondral lesions of the talus. Am J Sports Med 40(3):534–541. doi:10.1177/0363546511431238

    Article  PubMed  Google Scholar 

  • Miller Y, Bachowski G, Benjamin R, Eklund D, Hibbard A, Lightfoot T (2007) Practice guidelines for blood transfusion: a compilation from recent peer-reviewed literature, vol 56, 2nd edn. American Red Cross, Washington

    Google Scholar 

  • Mishra A, Tummala P, King A, Lee B, Kraus M, Tse V, Jacobs CR (2009) Buffered platelet-rich plasma enhances mesenchymal stem cell proliferation and chondrogenic differentiation. Tissue Eng Part C Methods 15(3):431–435. doi:10.1089/ten.tec.2008.0534

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miyamoto C, Matsumoto T, Sakimura K, Shindo H (2007) Osteogenic protein-1 with transforming growth factor-beta1: potent inducer of chondrogenesis of synovial mesenchymal stem cells in vitro. J Orthop Sci 12(6):555–561. doi:10.1007/s00776-007-1176-4

    Article  CAS  PubMed  Google Scholar 

  • Moore EE, Bendele AM, Thompson DL, Littau A, Waggie KS, Reardon B, Ellsworth JL (2005) Fibroblast growth factor-18 stimulates chondrogenesis and cartilage repair in a rat model of injury-induced osteoarthritis. Osteoarthritis Cartilage 13(7):623–631. doi:10.1016/j.joca.2005.03.003

    Article  CAS  PubMed  Google Scholar 

  • Morales TI (2008) The quantitative and functional relation between insulin-like growth factor-I (IGF) and IGF-binding proteins during human osteoarthritis. J Orthop Res 26(4):465–474. doi:10.1002/jor.20549

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nakanishi T, Nishida T, Shimo T, Kobayashi K, Kubo T, Tamatani T, Tezuka K, Takigawa M (2000) Effects of CTGF/Hcs24, a product of a hypertrophic chondrocyte-specific gene, on the proliferation and differentiation of chondrocytes in culture. Endocrinology 141(1):264–273. doi:10.1210/endo.141.1.7267

    Article  CAS  Google Scholar 

  • Nishida T, Nakanishi T, Asano M, Shimo T, Takigawa M (2000a) Effects of CTGF/Hcs24, a hypertrophic chondrocyte-specific gene product, on the proliferation and differentiation of osteoblastic cells in vitro. J Cell Physiol 184(2):197–206. doi:10.1002/1097-4652(200008)184:2<197::aid-jcp7>3.0.co;2-r

    Article  CAS  PubMed  Google Scholar 

  • Nishida Y, Knudson CB, Eger W, Kuettner KE, Knudson W (2000b) Osteogenic protein 1 stimulates cells-associated matrix assembly by normal human articular chondrocytes: up-regulation of hyaluronan synthase, CD44, and aggrecan. Arthritis Rheum 43(1):206–214. doi:10.1002/1529-0131(200001)43:1<206::aid-anr25>3.0.co;2-1

    Article  CAS  PubMed  Google Scholar 

  • Nishida T, Kubota S, Nakanishi T, Kuboki T, Yosimichi G, Kondo S, Takigawa M (2002) CTGF/Hcs24, a hypertrophic chondrocyte-specific gene product, stimulates proliferation and differentiation, but not hypertrophy of cultured articular chondrocytes. J Cell Physiol 192(1):55–63. doi:10.1002/jcp.10113

    Article  CAS  PubMed  Google Scholar 

  • Nishida T, Kubota S, Kojima S, Kuboki T, Nakao K, Kushibiki T, Tabata Y, Takigawa M (2004) Regeneration of defects in articular cartilage in rat knee joints by CCN2 (connective tissue growth factor). J Bone Miner Res 19(8):1308–1319. doi:10.1359/jbmr.040322

    Article  CAS  PubMed  Google Scholar 

  • Noh MJ, Copeland RO, Yi Y, Choi KB, Meschter C, Hwang S, Lim CL, Yip V, Hyun JP, Lee HY, Lee KH (2010) Pre-clinical studies of retrovirally transduced human chondrocytes expressing transforming growth factor-beta-1 (TG-C). Cytotherapy 12(3):384–393. doi:10.3109/14653240903470639

    Article  CAS  PubMed  Google Scholar 

  • Nurden AT, Nurden P, Sanchez M, Andia I, Anitua E (2008) Platelets and wound healing. Front Biosci 13:3532–3548

    PubMed  Google Scholar 

  • Pascual-Garrido C, Chubinskaya S (2015) Potential targets for pharmacologic therapies. In: Olson S, Guilak F (eds) Post-traumatic arthritis: pathogenesis, diagnosis, and management. Springer, pp 331–342

    Google Scholar 

  • Power J, Hernandez P, Guehring H, Getgood A, Henson F (2014) Intra-articular injection of rhFGF-18 improves the healing in microfracture treated chondral defects in an ovine model. J Orthop Res 32(5):669–676. doi:10.1002/jor.22580

    Article  CAS  PubMed  Google Scholar 

  • Qi BW, Yu AX, Zhu SB, Zhou M, Wu G (2013) Chitosan/poly(vinyl alcohol) hydrogel combined with Ad-hTGF-beta1 transfected mesenchymal stem cells to repair rabbit articular cartilage defects. Exp Biol Med (Maywood) 238(1):23–30. doi:10.1258/ebm.2012.012223

    Article  CAS  Google Scholar 

  • Roos H, Adalberth T, Dahlberg L, Lohmander LS (1995) Osteoarthritis of the knee after injury to the anterior cruciate ligament or meniscus: the influence of time and age. Osteoarthritis Cartilage 3(4):261–267

    Article  CAS  PubMed  Google Scholar 

  • Sanchez M, Fiz N, Azofra J, Usabiaga J, Aduriz Recalde E, Garcia Gutierrez A, Albillos J, Garate R, Aguirre JJ, Padilla S, Orive G, Anitua E (2012) A randomized clinical trial evaluating plasma rich in growth factors (PRGF-Endoret) versus hyaluronic acid in the short-term treatment of symptomatic knee osteoarthritis. Arthroscopy 28(8):1070–1078. doi:10.1016/j.arthro.2012.05.011

    Article  PubMed  Google Scholar 

  • Schalkwijk J, Joosten LA, van den Berg WB, van de Putte LB (1989) Chondrocyte nonresponsiveness to insulin-like growth factor 1 in experimental arthritis. Arthritis Rheum 32(7):894–900

    CAS  PubMed  Google Scholar 

  • Shen B, Wei A, Whittaker S, Williams LA, Tao H, Ma DD, Diwan AD (2010) The role of BMP-7 in chondrogenic and osteogenic differentiation of human bone marrow multipotent mesenchymal stromal cells in vitro. J Cell Biochem 109(2):406–416. doi:10.1002/jcb.22412

    CAS  PubMed  Google Scholar 

  • Shi S, Mercer S, Eckert GJ, Trippel SB. Growth factor regulation of growth factors in articular chondrocytes. J Biol Chem 2009;284:6697–6704

    Google Scholar 

  • Shimmin A, Young D, O’Leary S, Shih MS, Rueger DC, Walsh WR (2003) Growth factor augmentation of an ovine mosaicplasty model. Trans ICRS 4th Symposium, no. 16, Toronto

    Google Scholar 

  • Smyth SS, McEver RP, Weyrich AS, Morrell CN, Hoffman MR, Arepally GM, French PA, Dauerman HL, Becker RC (2009) Platelet functions beyond hemostasis. J Thromb Haemost 7(11):1759–1766. doi:10.1111/j.1538-7836.2009.03586.x

    Article  CAS  PubMed  Google Scholar 

  • Song JJ, Aswad R, Kanaan RA, Rico MC, Owen TA, Barbe MF, Safadi FF, Popoff SN (2007) Connective tissue growth factor (CTGF) acts as a downstream mediator of TGF-beta1 to induce mesenchymal cell condensation. J Cell Physiol 210(2):398–410. doi:10.1002/jcp.20850

    Article  CAS  PubMed  Google Scholar 

  • Sun Y, Feng Y, Zhang CQ, Chen SB, Cheng XG (2010) The regenerative effect of platelet-rich plasma on healing in large osteochondral defects. Int Orthop 34(4):589–597. doi:10.1007/s00264-009-0793-2

    Article  CAS  PubMed  Google Scholar 

  • Sundman EA, Cole BJ, Karas V, Della Valle C, Tetreault MW, Mohammed HO, Fortier LA (2014) The anti-inflammatory and matrix restorative mechanisms of platelet-rich plasma in osteoarthritis. Am J Sports Med 42(1):35–41. doi:10.1177/0363546513507766

    Article  PubMed  Google Scholar 

  • Tomita N, Hattori T, Itoh S, Aoyama E, Yao M, Yamashiro T, Takigawa M (2013) Cartilage-specific over-expression of CCN family member 2/connective tissue growth factor (CCN2/CTGF) stimulates insulin-like growth factor expression and bone growth. PLoS One 8(3):e59226. doi:10.1371/journal.pone.0059226

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vinall RL, Lo SH, Reddi AH (2002) Regulation of articular chondrocyte phenotype by bone morphogenetic protein 7, interleukin 1, and cellular context is dependent on the cytoskeleton. Exp Cell Res 272(1):32–44. doi:10.1006/excr.2001.5395

    Article  CAS  PubMed  Google Scholar 

  • Yan D, Chen D, Cool SM, van Wijnen AJ, Mikecz K, Murphy G, Im HJ (2011) Fibroblast growth factor receptor 1 is principally responsible for fibroblast growth factor 2-induced catabolic activities in human articular chondrocytes. Arthritis Res Ther 13(4):R130. doi:10.1186/ar3441

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhu S, Zhang B, Man C, Ma Y, Liu X, Hu J (2014) Combined effects of connective tissue growth factor-modified bone marrow-derived mesenchymal stem cells and NaOH-treated PLGA scaffolds on the repair of articular cartilage defect in rabbits. Cell Transplant 23(6):715–727. doi:10.3727/096368913x669770

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Midwest Orthopaedics at Rush, Rush University Medical Center, Chicago, IL, 60612, USA

    Maximilian A. Meyer, Atsushi Urita, Brian J. Cole & Susanna Chubinskaya

Authors
  1. Maximilian A. Meyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Atsushi Urita
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Brian J. Cole
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Susanna Chubinskaya
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Maximilian A. Meyer .

Editor information

Editors and Affiliations

  1. Orthopädische Klinik für die Universität Regensburg, Universitätsklinikum Regensburg, Regensburg, Germany

    Susanne Grässel

  2. Department of General, Trauma, and Reconstruction Surgery, Ludwig-Maximilians-University, Munich, Germany

    Attila Aszódi

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Meyer, M.A., Urita, A., Cole, B.J., Chubinskaya, S. (2017). Growth Factors in Cartilage Repair. In: Grässel, S., Aszódi, A. (eds) Cartilage. Springer, Cham. https://doi.org/10.1007/978-3-319-53316-2_6

Download citation

Publish with us

Policies and ethics

Search

Navigation