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Hyaluronan increases RANKL expression in bone marrow stromal cells through CD44
Jay J Cao1, Patrick A Singleton, Sharmila Majumdar
1Division of Endocrinology, Veterans Affairs Medical Center, San Francisco, California 94121, USA.
Summary
Hyaluronan (HA) activates CD44 to increase RANKL expression in bone marrow stromal cells. CD44-deficient mice show altered bone structure, indicating CD44’s role in bone metabolism.
Area of Science:
- Skeletal Biology and Bone Metabolism
- Extracellular Matrix Signaling
Background:
- Hyaluronan (HA), a key component of the bone marrow extracellular matrix, interacts with its receptor CD44.
- This interaction initiates intracellular signaling pathways influencing cell behavior and potentially bone metabolism.
Purpose of the Study:
- To investigate if HA-CD44 signaling affects Receptor Activator of Nuclear Factor kappa-B Ligand (RANKL) and Osteoprotegerin (OPG) expression.
- To determine the functional significance of CD44 in regulating bone metabolism.
Main Methods:
- Primary bone marrow stromal cells (BMSCs) from wildtype and CD44-deficient mice were cultured.
- Cells were treated with HA or anti-CD44 antibody; gene and protein expression (RANKL, OPG, CD44, ALP, OC, COLL) were analyzed.
- Bone structure was assessed using micro-CT and histomorphometry in vivo.
Main Results:
- HA dose-dependently increased RANKL mRNA and protein in BMSCs, an effect blocked by anti-CD44 antibody.
- CD44-deficient mice exhibited thicker cortical bone and smaller medullary cavities, with reduced RANKL expression.
- CD44-deficient cells did not respond to HA or anti-CD44 antibody, and bone resorption indices were unaffected at 7 weeks.
Conclusions:
- Hyaluronan activates CD44 to upregulate RANKL expression in bone marrow stromal cells.
- CD44 plays a crucial role in mediating HA's effects on RANKL and influences bone structure.