title: Mechanisms involved in enhancement of osteoclast formation and function by low molecular weight hyaluronic acid.
abstract: Hyaluronic acid (HA) is a component of the extracellular matrix that has been shown to play an important role in bone formation, resorption, and mineralization both in vivo and in vitro. We examined the effects of HA at several molecular weights on osteoclast formation and function induced by RANKL (receptor activator of NF-kappa B ligand) in a mouse monocyte cell line (RAW 264.7). HA at M(r) < 8,000 (low molecular weight HA (LMW-HA)) enhanced tartrate-resistant acid phosphatase-positive multinucleated cell formation and tartrate-resistant acid phosphatase activity induced by RANKL in a dose-dependent manner, whereas HA at M(r) > 900,000 (high molecular weight HA (HMW-HA)) showed no effect on osteoclast differentiation. LMW-HA enhanced pit formation induced by RAW 264.7 cells, whereas HMW-HA did not, and LMW-HA stimulated the expression of RANK (receptor activator of NF-kappa B) protein in RAW 264.7 cells. In addition, we found that LMW-HA enhanced the levels of c-Src protein and phosphorylation of ERKs and p38 MAPK in RAW 264.7 cells stimulated with RANKL, whereas the p38 MAPK inhibitor SB203580 inhibited RANKL-induced osteoclast differentiation. This enhancement of c-Src and RANK proteins induced by LMW-HA was inhibited by CD44 function-blocking monoclonal antibody. These results indicate that LMW-HA plays an important role in osteoclast differentiation and function through the interaction of RANKL and RANK.
authors.affiliation: Second Department of Oral and Maxillofacial Surgery, School of Dentistry, Kyushu Dental College, Kitakyushu, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Ariyoshi
authors.forename: Tetsu
authors.initials: T
authors.lastname: Takahashi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kanno
authors.forename: Hisashi
authors.initials: H
authors.lastname: Ichimiya
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takano
authors.forename: Takeyoshi
authors.initials: T
authors.lastname: Koseki
authors.forename: Tatsuji
authors.initials: T
authors.lastname: Nishihara
mesh_terms: D000135:Acid Phosphatase / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015153:Blotting, Western; D001862:Bone Resorption; D000081247:CSK Tyrosine-Protein Kinase; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005109:Extracellular Matrix / Q000378:metabolism; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D006820:Hyaluronic Acid / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D007527:Isoenzymes / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008970:Molecular Weight; D009000:Monocytes / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D015398:Signal Transduction; D000071681:Tartrate-Resistant Acid Phosphatase; D013997:Time Factors; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D019061:src-Family Kinases
chemical_list: D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D018960:Hyaluronan Receptors; D007093:Imidazoles; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D011725:Pyridines; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D006820:Hyaluronic Acid; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; C093642:SB 203580