Human osteoblasts express functional CXC chemokine receptors 3 and 5: activation by their ligands, CXCL10 and CXCL13, significantly induces alkaline phosphatase and beta-N-acetylhexosaminidase release.
Osteoblasts (OBs) contribute to the maintenance of bone homeostasis and their activity can be influenced by immune cells localized in bone lacunae. We investigated the expression of the chemokine receptors in isolated human OBs by reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometry, and report a novel finding, namely, that OBs express high levels of CXC chemokine receptor 3 (CXCR3) and 5 (CXCR5). Functional assays to evaluate CXCR3 and CXCR5 demonstrated that their ligands-CXCL10 and CXCL13, respectively-significantly induce the release of beta-N-acetylhexosaminidase, an enzyme involved in endochondral ossification and bone remodeling able to degrade important extracellular matrix components. Alkaline phosphatase activity, a useful index of matrix formation was also up-regulated by CXCL10 and CXCL13. However, OB activation by these ligands does not affect OB proliferation. Both Bordetella pertussis toxin and neutralizing anti-CXCR3/anti-CXCR5 monoclonal antibodies block CXCL10 and CXCL13 induction, respectively. We also demonstrated the expression of CXCL10 and CXCL13 in human bone tissue biopsies. These results indicate that both CXCR3/CXCL10 and CXCR5/CXCL13 receptor-ligand pairs may play an important role in OB activity through the specific up-regulation of two enzymes, which are involved in the bone remodeling process. Moreover, our data suggest that OBs may play a role in the modulation of bone formation through the combined action of these two enzymes.
Lisignoli
Gina
G
Laboratorio di Immunologia e Genetica, Istituti Ortopedici Rizzoli, Bologna, Italy.
Toneguzzi
Stefania
S
Piacentini
Anna
A
Cattini
Luca
L
Lenti
Anna
A
Tschon
Matilde
M
Cristino
Sandra
S
Grassi
Francesco
F
Facchini
Andrea
A
D000469:Alkaline Phosphatase / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D054357:Chemokine CXCL10; D054382:Chemokine CXCL13; D019743:Chemokines, CXC / Q000378:metabolism* / Q000494:pharmacology; D005089:Exocytosis / Q000276:immunology; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D010006:Osteoblasts / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology*; D010012:Osteogenesis / Q000187:drug effects / Q000276:immunology*; D054367:Receptors, CXCR3; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine / Q000187:drug effects / Q000378:metabolism*; D018121:Receptors, Cytokine / Q000187:drug effects / Q000378:metabolism*; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
C110663:CXCL13 protein, human; C515187:CXCR3 protein, human; C095085:CXCR5 protein, human; D054357:Chemokine CXCL10; D054382:Chemokine CXCL13; D019743:Chemokines, CXC; D054367:Receptors, CXCR3; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D000469:Alkaline Phosphatase; D001619:beta-N-Acetylhexosaminidases