Synovial fibroblasts and synovial macrophages from patients with rheumatoid arthritis and other inflammatory joint diseases show chromosomal aberrations

Abstract

Chromosomal aberrations were comparatively assessed in nuclei extracted from synovial tissue, primary-culture (P-0) synovial cells, and early-passage synovial fibroblasts (SFB; 98% enrichment; P-1, P-4 [passage 1, passage 4]) from patients with rheumatoid arthritis (RA; n = 21), osteoarthritis (OA; n = 24), and other rheumatic diseases. Peripheral blood lymphocytes (PBL) and skin fibroblasts (FB) (P-1, P-4) from the same patients, as well as SFB from normal joints and patients with joint trauma (JT) (n = 4), were used as controls. Analyses proceeded by standard GTG-banding and interphase centromere fluorescence in situ hybridization. Structural chromosomal aberrations were observed in SFB (P-1 or P-4) from 4 of 21 RA patients (19%), with involvement of chromosome 1 [e.g. del(1)(q12)] in 3 of 4 cases. In 10 of the 21 RA cases (48%), polysomy 7 was observed in P-1 SFB. In addition, aneusomies of chromosomes 4, 6, 8, 9, 12, 18, and Y were present. The percentage of polysomies was increased in P-4. Similar chromosomal aberrations were detected in SFB of OA and spondylarthropathy patients. No aberrations were detected in i) PBL or skin FB from the same patients (except for one OA patient with a karyotype 45,X[10]/46,XX[17] in PBL and variable polysomies in long-term culture skin FB); or ii) synovial tissue and/or P-1 SFB of normal joints or of patients with joint trauma. In conclusion, qualitatively comparable chromosomal aberrations were observed in synovial tissue and early-passage SFB of patients with RA, OA, and other inflammatory joint diseases. Thus, although of possible functional relevance for the pathologic role of SFB in RA, these alterations probably reflect a common response to chronic inflammatory stress in rheumatic diseases. DMEM = Dulbecco's modified Eagle's medium; FB = fibroblasts; FCS = fetal calf serum; FISH = fluorescence in situ hybridization; HEPES = N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid; IL = interleukin; ISCN = International System for Human Cytogenetic Nomenclature; JT = joint trauma; OA = osteoarthritis; P-0 = primary culture; P-1 = passage 1; P-4 = passage 4; PBL = peripheral blood lymphocytes; PBS = phosphate-buffered saline; RA = rheumatoid arthritis; RPMI = Roswell Park Memorial Institute [medium]; SFB = synovial fibroblasts.

Bone Marrow Mesenchymal Stem Cells: Biological Properties and Their Role in Hematopoiesis and Hematopoietic Stem Cell Transplantation

“…We thus suggested that trisomy 5 should be considered as a non-random in vitro event of unknown significance at present. On the other hand trisomy 7 has not been previously described in hematologic malignancies, but is a common finding in malignant and non-malignant tissues [147][148][149]. The frequency of trisomy 7 seems to increase with age and its presence might be associated with aging rather than with the disease per se [148].…”

Identification of intra-group, inter-individual, and gene-specific variances in mRNA expression profiles in the rheumatoid arthritis synovial membrane

“…Regarding internal molecular changes in the individuals, a participation of mutations or single nucleotide polymorphisms in different genes is plausible, either directly [ 45 , 46 ] or via mutated regulators (for example, transcription factors, mRNA stability modifiers, and so on [ 47 ]). This also includes broader genomic rearrangements (for example, chromosomal translocations or polysomies [ 48 , 49 ]) as well as epigenomic modifications (for example, gene/promoter methylation [ 50 ]). In addition, the individual composition of cell types in the analyzed SM samples may influence the mRNA expression profile, depending on the inflammatory status and/or cell proliferation, potentially resulting in enhanced immigration/proliferation of T cells, B cells, or synovial fibroblasts [ 51 ].…”

Somatic Mosaicism in Cases with Small Supernumerary Marker Chromosomes

“…After the introduction of molecular cytogenetics [4-7], it became even possible to analyze numerical chromosomal aberrations in non-dividing cells [8]. By that also low-level chromosomal aberrations could be detected in tumor [9-13], various clinical [14-18] and neuronal diseases [19-27], embryonic tissues [28-32] and different tissue types [9, 13, 15, 33-35]. Overall it can be stated that chromosome instability is one of the main causes of large-scale genome variation [36-39].…”