Blood-derived human osteoclast resorption activity is impaired by Hyaluronan-CD44 engagement via a p38-dependent mechanism

Eliana Pivetta, Martina Scapolan, Bruna Wassermann, Agostino Steffan, Alfonso Colombatti, Paola Spessotto

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The control of bone resorption is crucial in osteolytic diseases. Once attached to bone, osteoclasts (OCs) initiate the resorption process through the activation of a complex cascade of morphological and biochemical changes. Hyaluronan (HA), an extracellular glycosaminoglycan long non-branching polysaccharide, is expressed in bone matrices. Here we demonstrate that HA counter-balances the erosion activity of human mature OCs by significantly reducing their degradative potential. HA treatment of fully differentiated OCs derived from human peripheral blood monocytes inhibited migration on collagen as well as bone resorption. HA-mediated effects were primarily due to TRAcP, MMP-9, and cathepsin K down-regulation and to the increased levels of TIMP-1, a natural MMP-9 inhibitor. Binding of HA to mature OCs was entirely mediated by CD44: function-blocking anti-CD44 antibodies fully abrogated HA effects, and the engagement of HA receptor caused a rapid de-phosphorylation of Ser 325 in the CD44 cytoplasmic tail. The inhibitory action by HA was associated with a transient up-phosphorylation of Pyk2, a novel persistent phosphorylation of p38 and the down-regulation of NFATc1 transcription factor. Our results provide a direct evidence for the involvement of CD44 in the HA-dependent regulation of OC activity and suggest a signaling pathway that could be unique in OC function inhibition.

Original languageEnglish
Pages (from-to)769-779
Number of pages11
JournalJournal of Cellular Physiology
Volume226
Issue number3
DOIs
Publication statusPublished - Mar 2011

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Osteoclasts
Hyaluronic Acid
Blood
Phosphorylation
Bone
Bone Resorption
Matrix Metalloproteinases
Down-Regulation
CD44 Antigens
Cathepsin K
Bone Matrix
Tissue Inhibitor of Metalloproteinase-1
Blocking Antibodies
Matrix Metalloproteinase Inhibitors
Glycosaminoglycans
Human Activities
Polysaccharides
Tail
Monocytes
Anti-Idiotypic Antibodies

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Blood-derived human osteoclast resorption activity is impaired by Hyaluronan-CD44 engagement via a p38-dependent mechanism. / Pivetta, Eliana; Scapolan, Martina; Wassermann, Bruna; Steffan, Agostino; Colombatti, Alfonso; Spessotto, Paola.

In: Journal of Cellular Physiology, Vol. 226, No. 3, 03.2011, p. 769-779.

Research output: Contribution to journalArticle

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