Expression and pathological effects of periostin in human osteoarthritis cartilage.
BACKGROUND
Osteoarthritis (OA) is one of the most common joint diseases in elderly people, however, the underlying mechanism of OA pathogenesis is not completely clear. Periostin, the extracellular protein, has been shown by cDNA array analysis to be highly expressed in OA, but its function is not fully understood. The purpose of this study was to examine the expression and function of periostin in human OA.


METHODS
Human cartilage and synovia samples were used for the analysis of periostin expression and function. The human cartilage samples were obtained from the knees of patients undergoing total knee arthroplasty as OA samples and from the femoral bone head of patients with femoral neck fracture as control samples. Quantitative RT-PCR, ELISA, and immunohistochemistry were used for analysis of periostin expression in cartilage and synovia. Human primary chondrocytes isolated from control cartilage were stimulated by periostin, and the alteration of OA related gene expression was examined using quantitative RT-PCR. Immunocytochemistry of p65 was performed for the analysis of nuclear factor kappa B (NFκB) activation.


RESULTS
The periostin mRNA was significantly higher in OA cartilage than in control cartilage. Immunohistochemical analysis of periostin showed that the main positive signal was localized in chondrocytes and their periphery matrix near the erosive area, with less immunoreactivity in deeper zones. There was positive correlation between Mankin score and periostin immunoreactivity. The periostin expression was also detected in the fibrotic cartilage and tissue of subchondral bone. In cultured human chondrocytes, periostin induced the expression of interleukin (IL)-6, IL-8, matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, and nitric oxide synthase-2 (NOS2) in a dose- and time-dependent manner. The activation of NFκB signaling was recognized by the nuclear translocation of p65. Periostin-induced upregulation of these genes was suppressed by NFκB inactivation in chondrocytes.


CONCLUSIONS
Periostin was upregulated in OA cartilage, and it may amplify inflammatory events and accelerate OA pathology.
Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, Japan. rchijimatsu@ort.med.osaka-u.ac.jp.|Department of Orthopaedic Surgery, Osaka University Graduate School of Frontier Bio Science, 2-2 Yamadaoka, Suita, Osaka, Japan. rchijimatsu@ort.med.osaka-u.ac.jp.
Ryota
R
Chijimatsu
Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, Japan. kunugiza@ort.med.osaka-u.ac.jp.|Department of Orthopaedic Surgery, Japan Community Healthcare Organization Hoshigaoka Medical Center, 4-8-1 Hoshigaoka, Hirakata, Osaka, Japan. kunugiza@ort.med.osaka-u.ac.jp.
Yasuo
Y
Kunugiza
Department of Clinical Gene Therapy, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, Japan. taniyama@cgt.med.osaka-u.ac.jpl.
Yoshiaki
Y
Taniyama
Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, Japan. n-nakamura@ort.med.osaka-u.ac.jp.|Department of Rehabilitation Science, Osaka Health Science University, 1-9-27 Kita-ku Tenma, Osaka, Japan. n-nakamura@ort.med.osaka-u.ac.jp.
Norimasa
N
Nakamura
Department of Orthopaedic Biomaterial Science, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, Japan. tomita@ort.med.osaka-u.ac.jp.
Tetsuya
T
Tomita
Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, Japan. yhideki@ort.med.osaka-u.ac.jp.
Hideki
H
Yoshikawa
D000368:Aged; D000369:Aged, 80 and over; D002356:Cartilage / Q000378:metabolism* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D020782:Matrix Metalloproteinases / Q000096:biosynthesis / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000235:genetics; D010003:Osteoarthritis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
D015815:Cell Adhesion Molecules; D007378:Interleukins; D016328:NF-kappa B; C512835:POSTN protein, human; D012333:RNA, Messenger; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D020782:Matrix Metalloproteinases