title: CXCL12 (SDF-1) and CXCL13 (BCA-1) chemokines significantly induce proliferation and collagen type I expression in osteoblasts from osteoarthritis patients.
abstract: To evaluate the role of CXC chemokines CXCL8 (IL8), CXCL10 (IP-10), CXCL12 (SDF-1), and CXCL13 (BCA-1) in bone remodeling, we analyzed their effects on osteoblasts (OBs) obtained from subchondral trabecular bone tissue of osteoarthritis (OA) and post-traumatic (PT) patients. The expression of CXC receptors/ligands (CXCR1/CXCL8, CXCR2/CXCL8, CXCR3/CXCL10, CXCR4/CXCL12, and CXCR5/CXCL13) was analyzed in cultured OBs by flow cytometry and immunocytochemistry. Functional assays on CXC chemokine-treated-OBs in the presence or absence of their specific inhibitors were performed to analyze cellular proliferation and the enzymatic response to chemokine activation. The expression of chemokine ligands/receptors was also confirmed in bone tissue samples by immunohistochemical analysis. Collagen type I and alkaline phosphatase mRNA expression were analyzed on CXCL12- and CXCL13-treated OBs by real-time PCR. OBs from both OA and PT patients expressed high levels of CXCR3 and CXCR5 and lower amounts of CXCR1 and CXCR4. CXCL12 and CXCL13, only in OBs from OA patients, induced a significant proliferation that was also confirmed by specific blocking experiments. Moreover, OBs from OA patients released a higher amount of CXCL13 than those of PT patients while no differences were found for CXCL12. In the remodeling area of bone tissue samples, immunohistochemical analysis confirmed that OBs expressed CXCL12/CXCR4 and CXCL13/CXCR5 both in OA and PT samples. CXCL12 and CXCL13 upregulated collagen type I mRNA expression in OBs from OA patients. These data suggest that CXCL12 and CXCL13 may directly modulate cellular proliferation and collagen type I in OA patients, so contributing to the remodeling process that occurs in the evolution of this disease.
authors.affiliation: Laboratorio di Immunologia e Genetica, Istituti Ortopedici Rizzoli, Bologna, Italy. labimge@alma.unibo.it
authors.forename: Gina
authors.initials: G
authors.lastname: Lisignoli
authors.forename: Stefania
authors.initials: S
authors.lastname: Toneguzzi
authors.forename: Anna
authors.initials: A
authors.lastname: Piacentini
authors.forename: Sandra
authors.initials: S
authors.lastname: Cristino
authors.forename: Francesco
authors.initials: F
authors.lastname: Grassi
authors.forename: Carola
authors.initials: C
authors.lastname: Cavallo
authors.forename: Andrea
authors.initials: A
authors.lastname: Facchini
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D054357:Chemokine CXCL10; D054377:Chemokine CXCL12; D054382:Chemokine CXCL13; D019743:Chemokines, CXC / Q000378:metabolism*; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism*; D005089:Exocytosis / Q000502:physiology; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology*; D010641:Phenotype; D011485:Protein Binding; D019707:Receptors, Chemokine / Q000378:metabolism; D013977:Tibia / Q000166:cytology / Q000293:injuries; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
chemical_list: C114753:CXCL10 protein, human; C515255:CXCL12 protein, human; C110663:CXCL13 protein, human; D054357:Chemokine CXCL10; D054377:Chemokine CXCL12; D054382:Chemokine CXCL13; D019743:Chemokines, CXC; D024042:Collagen Type I; D016209:Interleukin-8; D019707:Receptors, Chemokine; D000469:Alkaline Phosphatase; D001619:beta-N-Acetylhexosaminidases