Intra-articular injection of hyaluronan restores the aberrant expression of matrix metalloproteinase-13 in osteoarthritic subchondral bone.
Subchondral bone is a candidate for treatment of osteoarthritis (OA). We investigated the effects of intra-articular injection of hyaluronan (IAI-HA) on subchondral bone in rabbit OA model. OA was induced by anterior cruciate ligament transection, with some rabbits receiving IAI-HA. OA was graded morphologically, and expression of mRNA was assessed by real-time RT-PCR. Tissue sections were stained with hyaluronan-binding protein, and penetration of fluorescent hyaluronan was assessed. The in vitro inhibitory effect of hyaluronan on MMP-13 was analyzed in human osteoarthritic subchondral bone osteoblasts (OA Ob) by real-time RT-PCR and ELISA. Binding of hyaluronan to OA Ob via CD44 was assessed by immunofluorescence cytochemistry. Expression of MMP-13 and IL-6 mRNA in cartilage and subchondral bone, and morphological OA grade, increased over time. IAI-HA ameliorated the OA grade and selectively suppressed MMP-13 mRNA in subchondral bone. IAI-HA enhanced the hyaluronan staining of subchondral bone marrow cells and osteocyte lacunae. Fluorescence was observed in the subchondral bone marrow space. In OA Ob, hyaluronan reduced the expression and production of MMP-13, and anti-CD44 antibody blocked hyaluronan binding to OA Ob. These findings indicate that regulation of MMP-13 in subchondral bone may be a critical mechanism during IAI-HA.
Hiraoka
Nobuyuki
N
Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. hiraoka@koto.kpu-m.ac.jp
Takahashi
Kenji A
KA
Arai
Yuji
Y
Sakao
Kei
K
Mazda
Osam
O
Kishida
Tsunao
T
Honjo
Kuniaki
K
Tanaka
Sakae
S
Kubo
Toshikazu
T
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000493:pharmacokinetics* / Q000494:pharmacology; D007270:Injections, Intra-Articular; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D053509:Matrix Metalloproteinase 13 / Q000235:genetics* / Q000378:metabolism; D020370:Osteoarthritis, Knee / Q000188:drug therapy* / Q000503:physiopathology; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D055675:Viscosupplements / Q000493:pharmacokinetics* / Q000494:pharmacology
C497483:CD44 protein, human; D018960:Hyaluronan Receptors; C508600:IL6 protein, human; D015850:Interleukin-6; D012333:RNA, Messenger; D055675:Viscosupplements; D006820:Hyaluronic Acid; D053509:Matrix Metalloproteinase 13