Reduction of Matrix Metalloprotease 3 in Rheumatoid Arthritis Rat by Low Level Diode Laser Irradiation

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Rheumatoid arthritis (RA) is an inflammatory joint disorder, whose progression leads to the destruction of cartilage and bone. Low-level laser irradiation (LLLI) is currently being evaluated for the treatment of RA ; however, the molecular mechanisms underlying its effectiveness remain unclear. To understand the anti-inflammatory effect of LLLI, we used the collagen-induced RA rat (CIA) model, and analyzed the gene expression profile in synovial membrane in knee joints. Total RNA was isolated from the synovial membrane tissue of CIA rat joints or CIA joints treated with LLLI (830 nm Ga-Al-As diode laser), and gene expression profiles were analyzed by DNA microarray (41,000 rat genes) and Ingenuity Pathway Analysis system (IPA). The mRNA levels were confirmed by reverse transcription polymerase chain reaction (RT-PCR) and real-time PCR. Proteins expression was also carried out by immunohistochemistry. DNA microarray and IPA network/canonical pathway analysis showed that matrix metalloproteases (MMPs) signaling was involved, among MMPs, MMP3 gene expression was increased in CIA tissue, and LLLI significantly decreased the gene expressio. The DNA microarray data of these mRNA levels were further validated and confirmed using RT-PCR and real-time PCR. Immunohistochemical study also demonstrated the reduction of MMP2 protein level by LLLI. Since MMP3 These findings suggest that inhibitory effect of MMP3 expression may be a part of decreased CXCL1 and ICAM1-1 expressions may be a part of the mechanisms in LLLI-mediated reduction of RA inflammation.