Hyaluronan inhibits osteoclast differentiation via Toll-like receptor 4
Open Access
- 1 January 2007
- journal article
- Published by The Company of Biologists in Journal of Cell Science
- Vol. 120 (1), 166-176
- https://doi.org/10.1242/jcs.03310
Abstract
The differentiation of osteoclasts, cells specialized for bone resorption, is governed by two key factors, macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor κB ligand (RANKL). The extracellular matrix (ECM) is an important factor influencing cell fate. To date, little investigation on the relationship between ECM components and osteoclast differentiation has been documented. In this study, we uncovered a potent anti-osteoclastogenic effect of hyaluronan (HA), an ECM component present in bone marrow and soft connective tissues, in primary mouse and human osteoclast precursor cell cultures. The anti-osteoclastogenic function of HA was dependent on Toll-like receptor 4 (TLR4) but not on CD44. HA inhibited M-CSF-dependent signaling pathways involving Rac, reactive oxygen species and mitogen-activated protein kinases, resulting in suppression of transcription factors AP-1 and MITF that control RANK expression. Furthermore, in an in vivo mouse model of calvarial bone resorption assays HA reduced RANKL-induced bone erosion and osteoclastogenesis. Our results clearly show that HA inhibits osteoclast differentiation through TLR4 by interfering with M-CSF signaling, and point that the interaction between ECM components and innate immune receptors can play an important role in the regulation of bone metabolism.Keywords
This publication has 42 references indexed in Scilit:
- The hematopoietic transcription factor PU.1 regulates RANK gene expression in myeloid progenitorsBiochemical and Biophysical Research Communications, 2005
- Hyaluronan Increases RANKL Expression in Bone Marrow Stromal Cells Through CD44Journal of Bone and Mineral Research, 2005
- Effect of CD44 deficiency on in vitro and in vivo osteoclast formationJournal of Cellular Biochemistry, 2004
- CD44 and hyaluronic acid cooperate with SDF-1 in the trafficking of human CD34+ stem/progenitor cells to bone marrowPublished by American Society of Hematology ,2004
- The effect of hyaluronan on osteoblast proliferation and differentiation in rat calvarial‐derived cell culturesJournal of Biomedical Materials Research Part A, 2003
- Rho-dependent Rho Kinase Activation Increases CD44 Surface Expression and Bone Resorption in OsteoclastsPublished by Elsevier BV ,2003
- Membrane Rafts Play a Crucial Role in Receptor Activator of Nuclear Factor κB Signaling and Osteoclast FunctionJournal of Biological Chemistry, 2003
- Oligosaccharides of Hyaluronan Activate Dendritic Cells via Toll-like Receptor 4The Journal of Experimental Medicine, 2002
- Linkage of M-CSF Signaling to Mitf, TFE3, and the Osteoclast Defect in Mitfmi/mi MiceMolecular Cell, 2001
- Role of colony‐stimulating factor‐1 in bone metabolismJournal of Cellular Biochemistry, 1994