Bone Abstracts (2014) 3 PP292 | DOI: 10.1530/boneabs.3.PP292

CXCL8 and CCL20 enhance osteoblast-mediated osteoclastogenesis

Janak L Pathak1, Astrid D Bakker1, Patrick Verschueren2, Willem F Lems3, Frank P Luyten2, Jenneke Klein-Nulend1 & Nathalie Bravenboer4


1Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, MOVE Research Institute Amsterdam, Amsterdam, The Netherlands; 2Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium; 3Department of Rheumatology, VU University Medical Center, MOVE Research Institute Amsterdam, Amsterdam, The Netherlands; 4Department of Clinical Chemistry, VU University Medical Center, MOVE Research Institute Amsterdam, Amsterdam, The Netherlands.


Osteoporosis is common in rheumatoid arthritis (RA). Since osteoblasts express receptors for CXCL8 and CCL20, which are produced by inflammatory cells around the inflamed joints in RA, we hypothesized that CXCL8 and CCL20 contribute to osteoporosis in RA by affecting osteoblast proliferation, differentiation, and osteoblast-osteoclast communication.

Primary human osteoblasts were cultured±CXCL8 (2–200 pg/ml) and CCL20 (5–500 pg/ml) for 14 days. Osteoblast proliferation and differentiation were analyzed. IL6 production was quantified by ELISA. Human peripheral blood mononuclear cells were cultured with conditioned medium from CXCL8 and CCL20-treated osteoblasts±IL6 inhibitor for 21 days. The number of TRACP-positive osteoclasts was counted, and osteoclast activity was determined by the resorption pit assay.

CXCL8 (200 pg/ml) enhanced mRNA expression of Ki-67 in osteoblasts by upto 2.7-fold, ALP by 1.7-fold, and IL6 concentration by 1.2-fold. CXCL8-conditioned medium enhanced osteoclast number by 1.7-fold (three to five nuclei), and 3.0-fold (greater than five nuclei). IL6 inhibition reduced these numbers by 40%.

CCL20 (500 pg/ml) enhanced mRNA expression of Ki-67 in osteoblasts up to 2.5-fold, ALP by 1.6-fold, and IL6 concentration by 1.3-fold. CCL20-conditioned medium enhanced osteoclastogenesis by 1.3-fold (three to five nuclei), and 2.8-fold (greater than five nuclei), IL6 inhibition reduced these numbers by 30%. CCL20-conditioned medium increased osteoclast activity by 2.2-fold. Neither CXCL8 nor CCL20 directly affected osteoclastogenesis.

CXCL8 and CCL20 did not negatively affect osteoblast proliferation or differentiation. However, both CXCL8 and CLC20 enhanced osteoblast-mediated osteoclastogenesis, partly via stimulation of IL6 production, suggesting that CXCL8 and CCL20 contribute to localized and generalized osteoporosis in RA.

Article tools

My recent searches

No recent searches.

My recently viewed abstracts