Layilin, a talin-binding hyaluronan receptor, is expressed in human articular chondrocytes and synoviocytes and is down-regulated by interleukin-1β.
OBJECTIVE
Layilin (LAYN), a 55-kDa transmembrane protein with homology to C-type lectins, has been identified as a receptor of hyaluronan (HA). Interestingly, LAYN does not share any sequence homology with CD44, a primary HA receptor. The primary aim of our study was to examine the expression and potential function of LAYN in human articular chondrocytes and synoviocytes.


METHODS
Samples were obtained from patients undergoing joint arthroplasty. Cells were grown in vitro, then stimulated with interleukin (IL)-1β or tumor necrosis factor alpha (TNFα) for 24 h and the expression of LAYN was analyzed. To assess the function of LAYN, we transfected chondrocytes with siRNA against LAYN, treated them with HA and IL-1β, and then analyzed the production of matrix metalloproteinase (MMP)-1 and MMP-13 in the treated chrondrocytes.


RESULTS
The results showed that LAYN was constitutively expressed in human articular chondrocytes and synoviocytes and that IL-1β significantly suppressed the expression of LAYN in these cells. HA repressed IL-1β-induced MMP-1 and MMP-13 production in chondrocytes, but this was significantly abrogated in chondrocytes transfected with siRNA against LAYN.


CONCLUSIONS
Our results show that human chondrocytes express LAYN, a novel HA receptor, and that LAYN may contribute to the regulation of HA functions in the arthritic condition. Further investigation of the HA receptor may lead to the development of novel therapeutics to regulate HA signaling in inflammatory arthritis.
Department of Frontier Medicine, Institute of Medical Science, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki-shi, Kanagawa 216-8511, Japan. minmrt@aol.com
Minako
M
Murata
Kazuo
K
Yudoh
Hiroyuki
H
Shimizu
Moroe
M
Beppu
Hiroshi
H
Nakamura
Tomohiro
T
Kato
Kayo
K
Masuko
D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000601:surgery; D019644:Arthroplasty, Replacement, Hip; D019645:Arthroplasty, Replacement, Knee; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology; D053583:Interleukin-1beta / Q000494:pharmacology*; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism / Q000601:surgery; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D053583:Interleukin-1beta; C546934:LAYN protein, human; D037181:Lectins, C-Type; D014409:Tumor Necrosis Factor-alpha; D006820:Hyaluronic Acid; D053509:Matrix Metalloproteinase 13; D020781:Matrix Metalloproteinase 1