Growth Factor Signalling in Osteoarthritis

Overview

Journal Growth Factors

Publisher Informa Healthcare

Specialty Biology

Date 2019 Jan 10

PMID 30624091

Citations 31

Authors

Jian Huang

Lan Zhao

Di Chen

Affiliations

Soon will be listed here.

Abstract

Osteoarthritis (OA) is one of the most common diseases, affecting more than 10% of populations and thus creating immense socioeconomic burden. The pathological changes of OA involve the entire joint, which is composed of multiple types of tissues and cells, exemplified by cartilage degradation, subchondral bone thickening, osteophyte formation, synovium inflammation and hypertrophy, and ligament degeneration. As joint homeostasis requires a complex network of growth factors to regulate anabolic and catabolic events, the dysregulation of growth factor signalling would have negative impacts on structure and function of multiple joint tissues and eventually lead to the onset and progression of OA. In this review, we will discuss TGF-β, NGF, Hedgehog and Wnt, the four growth factors which have received extensive attention in the field of OA and clinical/translational interrogation about their application in OA therapies.

Citing Articles

Strategies for promoting neurovascularization in bone regeneration.

Li X, Zhao Y, Miao L, An Y, Wu F, Han J Mil Med Res. 2025; 12(1):9.

PMID: 40025573 PMC: 11874146. DOI: 10.1186/s40779-025-00596-1.

CRISPR-mediated Sox9 activation and RelA inhibition enhance cell therapy for osteoarthritis.

Zhao L, Lai Y, Jiao H, Li J, Lu K, Huang J Mol Ther. 2024; 32(8):2549-2562.

PMID: 38879753 PMC: 11405173. DOI: 10.1016/j.ymthe.2024.06.016.

Single Injection AAV2-FGF18 Gene Therapy Reduces Cartilage Loss and Subchondral Bone Damage in a Mechanically Induced Model of Osteoarthritis.

Hollander J, Goraltchouk A, Liu J, Xu E, Luppino F, McAlindon T Curr Gene Ther. 2024; 24(4):331-345.

PMID: 38783531 DOI: 10.2174/0115665232275532231213063634.

GPX7 reduces chondrocyte inflammation and extracellular matrix degradation triggered by IL‑1β, via a mechanism mediated by ferroptosis.

Chen B, Fu W, Jie C, Zhang G, Li Z, Liu Y Mol Med Rep. 2024; 30(1).

PMID: 38757339 PMC: 11129537. DOI: 10.3892/mmr.2024.13242.

Nerve growth factor receptor limits inflammation to promote remodeling and repair of osteoarthritic joints.

Zhao L, Lai Y, Jiao H, Huang J Nat Commun. 2024; 15(1):3225.

PMID: 38622181 PMC: 11018862. DOI: 10.1038/s41467-024-47633-6.

References

Morales T, Joyce M, Sobel M, Danielpour D, Roberts A . Transforming growth factor-beta in calf articular cartilage organ cultures: synthesis and distribution. Arch Biochem Biophys. 1991; 288(2):397-405. DOI: 10.1016/0003-9861(91)90212-2. View

Lee K, Song S, Hwang T, Yi Y, Oh I, Lee J . Regeneration of hyaline cartilage by cell-mediated gene therapy using transforming growth factor beta 1-producing fibroblasts. Hum Gene Ther. 2001; 12(14):1805-13. DOI: 10.1089/104303401750476294. View

DAngelo M, Yan Z, Nooreyazdan M, Pacifici M, Sarment D, Billings P . MMP-13 is induced during chondrocyte hypertrophy. J Cell Biochem. 2000; 77(4):678-93. View

Gong Y, Slee R, Fukai N, Rawadi G, Roman-Roman S, Reginato A . LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell. 2001; 107(4):513-23. DOI: 10.1016/s0092-8674(01)00571-2. View

Kobayashi T, Soegiarto D, Yang Y, Lanske B, Schipani E, McMahon A . Indian hedgehog stimulates periarticular chondrocyte differentiation to regulate growth plate length independently of PTHrP. J Clin Invest. 2005; 115(7):1734-42. PMC: 1143590. DOI: 10.1172/JCI24397. View

Zhen G, Wen C, Jia X, Li Y, Crane J, Mears S . Inhibition of TGF-β signaling in mesenchymal stem cells of subchondral bone attenuates osteoarthritis. Nat Med. 2013; 19(6):704-12. PMC: 3676689. DOI: 10.1038/nm.3143. View

Zhou J, Chen Q, Lanske B, Fleming B, Terek R, Wei X . Disrupting the Indian hedgehog signaling pathway in vivo attenuates surgically induced osteoarthritis progression in Col2a1-CreERT2; Ihhfl/fl mice. Arthritis Res Ther. 2014; 16(1):R11. PMC: 3978435. DOI: 10.1186/ar4437. View

Aloe L, Tuveri M, CARCASSI U, Levi-Montalcini R . Nerve growth factor in the synovial fluid of patients with chronic arthritis. Arthritis Rheum. 1992; 35(3):351-5. DOI: 10.1002/art.1780350315. View

Ivkovic A, Pascher A, Hudetz D, Maticic D, Jelic M, Dickinson S . Articular cartilage repair by genetically modified bone marrow aspirate in sheep. Gene Ther. 2010; 17(6):779-89. DOI: 10.1038/gt.2010.16. View

10.

DellAccio F, De Bari C, El Tawil N, Barone F, Mitsiadis T, ODowd J . Activation of WNT and BMP signaling in adult human articular cartilage following mechanical injury. Arthritis Res Ther. 2006; 8(5):R139. PMC: 1779445. DOI: 10.1186/ar2029. View

11.

van Beuningen H, Glansbeek H, van der Kraan P, van den Berg W . Osteoarthritis-like changes in the murine knee joint resulting from intra-articular transforming growth factor-beta injections. Osteoarthritis Cartilage. 1999; 8(1):25-33. DOI: 10.1053/joca.1999.0267. View

12.

Zhu M, Tang D, Wu Q, Hao S, Chen M, Xie C . Activation of beta-catenin signaling in articular chondrocytes leads to osteoarthritis-like phenotype in adult beta-catenin conditional activation mice. J Bone Miner Res. 2008; 24(1):12-21. PMC: 2640321. DOI: 10.1359/jbmr.080901. View

13.

Tchetina E, Squires G, Robin Poole A . Increased type II collagen degradation and very early focal cartilage degeneration is associated with upregulation of chondrocyte differentiation related genes in early human articular cartilage lesions. J Rheumatol. 2005; 32(5):876-86. View

14.

Hannan M, Felson D, Pincus T . Analysis of the discordance between radiographic changes and knee pain in osteoarthritis of the knee. J Rheumatol. 2000; 27(6):1513-7. View

15.

Tonge D, Pearson M, Jones S . The hallmarks of osteoarthritis and the potential to develop personalised disease-modifying pharmacological therapeutics. Osteoarthritis Cartilage. 2014; 22(5):609-21. DOI: 10.1016/j.joca.2014.03.004. View

16.

Chandrasekhar S, Harvey A . Transforming growth factor-beta is a potent inhibitor of IL-1 induced protease activity and cartilage proteoglycan degradation. Biochem Biophys Res Commun. 1988; 157(3):1352-9. DOI: 10.1016/s0006-291x(88)81024-6. View

17.

Petty B, Cornblath D, Adornato B, Chaudhry V, Flexner C, Wachsman M . The effect of systemically administered recombinant human nerve growth factor in healthy human subjects. Ann Neurol. 1994; 36(2):244-6. DOI: 10.1002/ana.410360221. View

18.

Scharstuhl A, Vitters E, van der Kraan P, van den Berg W . Reduction of osteophyte formation and synovial thickening by adenoviral overexpression of transforming growth factor beta/bone morphogenetic protein inhibitors during experimental osteoarthritis. Arthritis Rheum. 2003; 48(12):3442-51. DOI: 10.1002/art.11328. View

19.

van Beuningen H, Glansbeek H, van der Kraan P, van den Berg W . Differential effects of local application of BMP-2 or TGF-beta 1 on both articular cartilage composition and osteophyte formation. Osteoarthritis Cartilage. 1999; 6(5):306-17. DOI: 10.1053/joca.1998.0129. View

20.

Ruiz-Heiland G, Horn A, Zerr P, Hofstetter W, Baum W, Stock M . Blockade of the hedgehog pathway inhibits osteophyte formation in arthritis. Ann Rheum Dis. 2012; 71(3):400-7. DOI: 10.1136/ard.2010.148262. View