C-X-C Motif Chemokine 12 Enhances Lipopolysaccharide-Induced Osteoclastogenesis and Bone Resorption In Vivo

Abstract

C-X-C motif chemokine 12 (CXCL12) belongs to the family of CXC chemokines. Lipopolysaccharide (LPS) induces inflammation-induced osteoclastogenesis and bone resorption, and in recent years, stimulatory effects of CXCL12 on bone resorption have also been reported. In the present study, we investigated the effects of CXCL12 on LPS-induced osteoclastogenesis and bone resorption. LPS was administered with or without CXCL12 onto mouse calvariae by daily subcutaneous injection. Numbers of osteoclasts and bone resorption were significantly elevated in mice co-administered LPS and CXCL12 compared with mice administered LPS alone. Moreover, receptor activator of NF-kB ligand (RANKL) and tumor necrosis factor-α (TNF-α) mRNA levels were higher in mice co-administered LPS and CXCL12 compared with mice administered LPS alone. These in vitro results confirmed a direct stimulatory effect of CXCL12 on RANKL- and TNF-α-induced osteoclastogenesis. Furthermore, TNF-α and RANKL mRNA levels were elevated in macrophages and osteoblasts, respectively, co-treated in vitro with CXCL12 and LPS, in comparison with cells treated with LPS alone. Our results suggest that CXCL12 enhances LPS-induced osteoclastogenesis and bone resorption in vivo through a combination of increasing LPS-induced TNF-α production by macrophages, increasing RANKL production by osteoblasts, and direct enhancement of osteoclastogenesis.

Docosahexaenoic Acid Inhibits Inflammation-Induced Osteoclast Formation and Bone Resorption in vivo Through GPR120 by Inhibiting TNF-α Production in Macrophages and Directly Inhibiting Osteoclast Formation

“…In a previous study, daily subcutaneous supracalvarial administration of 100 μg LPS to mouse calvariae for 5 days significantly induced osteoclast formation (37, 38). Therefore, we followed the same protocol, dose and LPS administration period in this study.…”

“…After dehydration, calvariae were embedded in paraffin and sectioned perpendicular to the sagittal suture (5-μm thickness) using a microtome (Leica, Wetzlar, Germany). Sections were stained for tartrate-resistant acid phosphatase (TRAP) and hematoxylin counterstain as previously described (37, 38). Osteoclasts were identified as TRAP-positive cells containing three or more nuclei.…”

“…Osteoclasts were identified as TRAP-positive cells containing three or more nuclei. The number of osteoclasts located at the mesenchyme of the sagittal suture was counted in all slides as described previously (37, 38). In addition, the percentage of interface of bone marrow space covered by osteoclasts and the number of osteoclast of interface of bone marrow space were histomorphometrically determined in specimens derived from each sample.…”

miR-142-5p as a CXCR4-Targeted MicroRNA Attenuates SDF-1-Induced Chondrocyte Apoptosis and Cartilage Degradation via Inactivating MAPK Signaling Pathway

“…erefore, in order to mimic the osteoarthritic environment of the knee joint, we treated the isolated chondrocytes with 100 ng/ml SDF-1 in each group [27]. As a receptor of SDF-1 [7], CXCR4 has been proven to be one of the key factors that are closely involved in the pathogenesis of OA [25,27,28].…”

“…erefore, in order to mimic the osteoarthritic environment of the knee joint, we treated the isolated chondrocytes with 100 ng/ml SDF-1 in each group [27]. As a receptor of SDF-1 [7], CXCR4 has been proven to be one of the key factors that are closely involved in the pathogenesis of OA [25,27,28]. e binding of SDF-1 to CXCR4 induces OA cartilage degeneration [28], and it also coordinates the crosstalk between subchondral bone and articular cartilage in OA pathogenesis [29].…”