Analysis of critical molecules and signaling pathways in osteoarthritis and rheumatoid arthritis

Xue,Feng; Zhang,Changqing; He,Zhimin; Ding,Liang; Xiao,Haijun

doi:10.3892/mmr.2012.1224

Analysis of critical molecules and signaling pathways in osteoarthritis and rheumatoid arthritis

Authors:
- Feng Xue
- Changqing Zhang
- Zhimin He
- Liang Ding
- Haijun Xiao
View Affiliations

Affiliations: Department of Orthopaedics, Fengxian Central Hospital, Shanghai 201400, P.R. China, Department of Orthopaedics, The Six People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200233, P.R. China
Published online on: December 4, 2012 https://doi.org/10.3892/mmr.2012.1224
Pages: 603-607

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Osteoarthritis (OA) and rheumatoid arthritis (RA) are the most prevalent forms of arthritis in the elderly. This study aimed to explore the molecular mechanisms of these diseases and identify underlying therapeutic targets. Using GSE1919 microarray data sets downloaded from the Gene Expression Omnibus database, we screened differentially expressed genes (DEGs) in OA and RA cells. The underlying molecular mechanisms of these crucial genes were investigated by Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Small molecule expression and SNP analysis were also conducted by searching CMap and dbSNP databases. More than 320 genes changed in the arthritic cells and there were only 196 DEGs between OA and RA. OA and RA activated the classic mitogen-activated protein kinase signaling pathway, insulin signaling pathway, antigen processing and presentation and intestinal immune network for IgA production. Graft-versus-host disease and autoimmune thyroid disease-related pathways were also activated in OA and RA. Parthenolide and alsterpaullone may be treatments for OA and RA and insulin-like growth factor 1, collagen α2(I) chain and special AT-rich sequence-binding protein 2 may be critical SNP molecules in arthritis. Our findings shed new light on the common molecular mechanisms of OA and RA and may provide theoretical support for further clinical therapeutic studies.

View Figures

View References

1	Roach HI: The complex pathology of osteoarthritis: even mitochondria are involved. Arthritis Rheum. 58:2217–2218. 2008. View Article : Google Scholar : PubMed/NCBI
2	Berenbaum F: New horizons and perspectives in the treatment of osteoarthritis. Arthritis Res Ther. 10(Suppl 2): S12008. View Article : Google Scholar : PubMed/NCBI
3	Dieppe P: Osteoarthritis of the knee in primary care. BMJ. 336:105–106. 2008. View Article : Google Scholar : PubMed/NCBI
4	Gay S, Gay RE and Koopman WJ: Molecular and cellular mechanisms of joint destruction in rheumatoid arthritis: two cellular mechanisms explain joint destruction? Ann Rheum Dis. 52(Suppl 1): S39–S47. 1993. View Article : Google Scholar : PubMed/NCBI
5	Kvien TK: Epidemiology and burden of illness of rheumatoid arthritis. Pharmacoeconomics. 22:1–12. 2004. View Article : Google Scholar : PubMed/NCBI
6	Beasley J: Osteoarthritis and rheumatoid arthritis: conservative therapeutic management. J Hand Ther. 25:163–171. 2012. View Article : Google Scholar : PubMed/NCBI
7	Scott DL and Symmons DP: The role of specialists in managing established rheumatoid arthritis. Rheumatology (Oxford). 47:237–238. 2008. View Article : Google Scholar : PubMed/NCBI
8	Biswas S, Manikandan J and Pushparaj PN: Decoding the differential biomarkers of Rheumatoid arthritis and Osteoarthritis: A functional genomics paradigm to design disease specific therapeutics. Bioinformation. 6:153–157. 2011. View Article : Google Scholar : PubMed/NCBI
9	Ungethuem U, Haeupl T, Witt H, et al: Molecular signatures and new candidates to target the pathogenesis of rheumatoid arthritis. Physiol Genomics. 42A:267–282. 2010. View Article : Google Scholar : PubMed/NCBI
10	Irizarry RA, Hobbs B, Collin F, et al: Exploration, normalization and summaries of high density oligonucleotide array probe level data. Biostatistics. 4:249–264. 2003. View Article : Google Scholar
11	Smyth GK: Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol. 3:32004.PubMed/NCBI
12	Benjamini Y and Hochberg Y: Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Series B Stat Methodol. 57:289–300. 1995.
13	Huang DW, Sherman BT and Lempicki RA: Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 4:44–57. 2009.PubMed/NCBI
14	Huang da W, Sherman BT and Lempicki RA: Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 37:1–13. 2009.PubMed/NCBI
15	Lamb J, Crawford ED, Peck D, et al: The connectivity map: using gene-expression signatures to connect small molecules, genes and disease. Science. 313:1929–1935. 2006. View Article : Google Scholar
16	Sondergaard BC, Schultz N, Madsen SH, Bay-Jensen AC, Kassem M and Karsdal MA: MAPKs are essential upstream signaling pathways in proteolytic cartilage degradation-divergence in pathways leading to aggrecanase and MMP-mediated articular cartilage degradation. Osteoarthritis Cartilage. 18:279–288. 2010. View Article : Google Scholar
17	Lawrence MC, Jivan A, Shao C, et al: The roles of MAPKs in disease. Cell Res. 18:436–442. 2008. View Article : Google Scholar : PubMed/NCBI
18	Kotovuori A, Pessa-Morikawa T, Kotovuori P, Nortamo P and Gahmberg CG: ICAM-2 and a peptide from its binding domain are efficient activators of leukocyte adhesion and integrin affinity. J Immunol. 162:6613–6620. 1999.PubMed/NCBI
19	Kaplan R, Morse B, Huebner K, et al: Cloning of three human tyrosine phosphatases reveals a multigene family of receptor-linked protein-tyrosine-phosphatases expressed in brain. Proc Natl Acad Sci U S A. 87:7000–7004. 1990. View Article : Google Scholar
20	Wang A and Dennis EA: Mammalian lysophospholipases. Biochim Biophys Acta. 1439:1–16. 1999. View Article : Google Scholar
21	Peyrard M, Fransson I, Xie YG, et al: Characterization of a new member of the human beta-adaptin gene family from chromosome 22q12, a candidate meningioma gene. Hum Mol Genet. 3:1393–1399. 1994. View Article : Google Scholar : PubMed/NCBI
22	Ferrara JL, Levine JE, Reddy P and Holler E: Graft-versus-host disease. Lancet. 373:1550–1561. 2009. View Article : Google Scholar : PubMed/NCBI
23	Weetman AP and McGregor AM: Autoimmune thyroid disease: further developments in our understanding. Endocr Rev. 15:788–830. 1994.PubMed/NCBI
24	López-Franco O, Hernández-Vargas P, Ortiz-Muñoz G, et al: Parthenolide modulates the NF-kappaB-mediated inflammatory responses in experimental atherosclerosis. Arterioscler Thromb Vasc Biol. 26:1864–1870. 2006.PubMed/NCBI
25	Yip KH, Zheng MH, Feng HT, Steer JH, Joyce DA and Xu J: Sesquiterpene lactone parthenolide blocks lipopolysaccharide-induced osteolysis through the suppression of NF-kappaB activity. J Bone Miner Res. 19:1905–1916. 2004. View Article : Google Scholar : PubMed/NCBI
26	Guzman ML, Rossi RM, Karnischky L, et al: The sesquiterpene lactone parthenolide induces apoptosis of human acute myelogenous leukemia stem and progenitor cells. Blood. 105:4163–4169. 2005. View Article : Google Scholar : PubMed/NCBI
27	Miglietta A, Bozzo F, Gabriel L and Bocca C: Microtubule-interfering activity of parthenolide. Chem Biol Interact. 149:165–173. 2004. View Article : Google Scholar : PubMed/NCBI
28	Feltenstein MW, Schuhly W, Warnick JE, Fischer NH and Sufka KJ: Anti-inflammatory and anti-hyperalgesic effects of sesquiterpene lactones from Magnolia and Bear’s foot. Pharmacol Biochem Behav. 79:299–302. 2004.PubMed/NCBI
29	Tiuman TS, Ueda-Nakamura T, Garcia Cortez DA, et al: Antileishmanial activity of parthenolide, a sesquiterpene lactone isolated from Tanacetum parthenium. Antimicrob Agents Chemother. 49:176–182. 2005. View Article : Google Scholar : PubMed/NCBI
30	Leost M, Schultz C, Link A, et al: Paullones are potent inhibitors of glycogen synthase kinase-3beta and cyclin-dependent kinase 5/p25. Eur J Biochem. 267:5983–5994. 2000. View Article : Google Scholar : PubMed/NCBI
31	Lahusen T, De Siervi A, Kunick C and Senderowicz AM: Alsterpaullone, a novel cyclin-dependent kinase inhibitor, induces apoptosis by activation of caspase-9 due to perturbation in mitochondrial membrane potential. Mol Carcinog. 36:183–194. 2003. View Article : Google Scholar
32	Hoppener JW, de Pagter-Holthuizen P, Geurts van Kessel AH, et al: The human gene encoding insulin-like growth factor I is located on chromosome 12. Hum Genet. 69:157–160. 1985. View Article : Google Scholar : PubMed/NCBI
33	Jansen M, van Schaik FM, Ricker AT, et al: Sequence of cDNA encoding human insulin-like growth factor I precursor. Nature. 306:609–611. 1983. View Article : Google Scholar : PubMed/NCBI
34	Studer RK: Nitric oxide decreases IGF-1 receptor function in vitro; glutathione depletion enhances this effect in vivo. Osteoarthritis Cartilage. 12:863–869. 2004. View Article : Google Scholar : PubMed/NCBI
35	Retief E, Parker MI and Retief AE: Regional chromosome mapping of human collagen genes alpha 2(I) and alpha 1(I) (COLIA2 and COLIA1). Hum Genet. 69:304–308. 1985. View Article : Google Scholar : PubMed/NCBI
36	Wenstrup RJ, Cohn DH, Cohen T and Byers PH: Arginine for glycine substitution in the triple-helical domain of the products of one alpha 2(I) collagen allele (COL1A2) produces the osteogenesis imperfecta type IV phenotype. J Biol Chem. 263:7734–7740. 1988.
37	Kikuno R, Nagase T, Ishikawa K, et al: Prediction of the coding sequences of unidentified human genes. XIV The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 6:197–205. 1999. View Article : Google Scholar
38	FitzPatrick DR, Carr IM, McLaren L, et al: Identification of SATB2 as the cleft palate gene on 2q32-q33. Hum Mol Genet. 12:2491–2501. 2003. View Article : Google Scholar : PubMed/NCBI