Stimulation of osteoclast migration and bone resorption by C–C chemokine ligands 19 and 21

Park, Cheol‐Kyu; Kim, Hyung Joon; Lee, Yong Deok; Lee, Zang Hee; Song, Yeong Wook; Kim, Hong Hee

doi:10.1038/emm.2017.100

Cited by 41 publications

(30 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The results suggest that the increased mobility of each osteoclast may amplify matrix‐resorbing activity. This is consistent with a recent report showing that chemokine pathways that activate RhoA and ROCK increase bone resorption in culture without increasing the osteoclast number . To test if the Pfn1 ‐KD osteoclasts are indeed more potent in bone resorption, we knocked down the Pfn1 on bone marrow cells.…”

Section: Resultssupporting

confidence: 88%

“…This is consistent with a recent report showing that chemokine pathways that activate RhoA and ROCK increase bone resorption in culture without increasing the osteoclast number. (25) To test if the Pfn1-KD osteoclasts are indeed more potent in bone resorption, we knocked down the Pfn1 on bone marrow cells. By evaluating the pit formation after 6 days of osteoclast induction, we found that the Pfn1-KD osteoclasts resorb more mineralized matrix than those transfected with control siRNA (Supplemental Fig.…”

Section: Pfn1-kd Affects Osteoclast Migration and Matrix Resorptionmentioning

confidence: 99%

See 1 more Smart Citation

Profilin 1 Negatively Regulates Osteoclast Migration in Postnatal Skeletal Growth, Remodeling, and Homeostasis in Mice

et al. 2019

View full text Add to dashboard Cite

Profilin 1 (Pfn1), a regulator of actin polymerization, controls cell movement in a context‐dependent manner. Pfn1 supports the locomotion of most adherent cells by assisting actin‐filament elongation, as has been shown in skeletal progenitor cells in our previous study. However, because Pfn1 has also been known to inhibit migration of certain cells, including T cells, by suppressing branched‐end elongation of actin filaments, we hypothesized that its roles in osteoclasts may be different from that of osteoblasts. By investigating the osteoclasts in culture, we first verified that Pfn1‐knockdown (KD) enhances bone resorption in preosteoclastic RAW264.7 cells, despite having a comparable number and size of osteoclasts. Pfn1‐KD in bone marrow cells showed similar results. Mechanistically, Pfn1‐KD osteoclasts appeared more mobile than in controls. In vivo, the osteoclast‐specific conditional Pfn1‐deficient mice (Pfn1‐cKO) by CathepsinK‐Cre driver demonstrated postnatal skeletal phenotype, including dwarfism, craniofacial deformities, and long‐bone metaphyseal osteolytic expansion, by 8 weeks of age. Metaphyseal and diaphyseal femurs were drastically expanded with suppressed trabecular bone mass as indicated by μCT analysis. Histologically, TRAP‐positive osteoclasts were increased at endosteal metaphysis to diaphysis of Pfn1‐cKO mice. The enhanced movement of Pfn1‐cKO osteoclasts in culture was associated with a slight increase in cell size and podosome belt length, as well as an increase in bone‐resorbing activity. Our study, for the first time, demonstrated that Pfn1 has critical roles in inhibiting osteoclast motility and bone resorption, thereby contributing to essential roles in postnatal skeletal homeostasis. Our study also provides novel insight into understanding skeletal deformities in human disorders. © 2018 American Society for Bone and Mineral Research.

show abstract

Section: Resultssupporting

confidence: 88%

Section: Pfn1-kd Affects Osteoclast Migration and Matrix Resorptionmentioning

confidence: 99%

Profilin 1 Negatively Regulates Osteoclast Migration in Postnatal Skeletal Growth, Remodeling, and Homeostasis in Mice

et al. 2019

View full text Add to dashboard Cite

show abstract

“…69,70 Likewise, CCL19 and CCL21 were reported to be higher in RA patients in comparison to osteoarthritis individuals. 69,71 Also, CCL19 has been found at high concentrations in the synovium where it was reported to be expressed by fibroblasts and macrophages. 69,70 In addition, inflammatory molecules such as lipopolysaccharide, TNF-α and IL-1β were found to promote CCR7 expression.…”

Section: Chemokines In Rheumatoid Arthritismentioning

confidence: 99%

“…69,70 In addition, inflammatory molecules such as lipopolysaccharide, TNF-α and IL-1β were found to promote CCR7 expression. 71 Moreover, CCL19 and CCL21 stimulated osteoclast migration as well as bone resorption by osteoclasts in an animal model of RA, 71 and CCL21 drives osteoclastogensis in RA through M1 macrophage polarization of Th17 cells as well as neovascularization. 68 CCL25 and its receptor CCR9 were both detected in the RA synovium.…”

Section: Chemokines In Rheumatoid Arthritismentioning

confidence: 99%

<p>Role of Chemokines and Chemokine Receptors in Rheumatoid Arthritis</p>

Elemam¹,

Hannawi

Maghazachi³

2020

ITT

View full text Add to dashboard Cite

Rheumatoid arthritis (RA) is one of the most prevalent autoimmune diseases and a prototypic inflammatory disease, affecting the small joints of the hands and feet. Chemokines and chemokine receptors play a critical role in RA pathogenesis via immune cells recruitment. Several chemokines and chemokine receptors are abundant in the peripheral blood and in the local inflamed joints of RA. Furthermore, synthetic and biologics disease modifying anti rheumatic drugs have been reported to affect chemokines expression. Thus, many studies have focused on targeting chemokines and chemokine receptors, where some have shown positive promising results. However, most of the chemokine blockers in human trials of RA treatment displayed some failures that can be attributed to several reasons in their structures and binding affinities. Nevertheless, targeting chemokines will continue to be under development, in order to improve their therapeutic potentials in RA and other autoimmune diseases. In this review we provide an up-to-date knowledge regarding the role of chemokines and chemokine receptors in RA with an emphasis on their activities on immune cells. We also discussed the effects of drugs targeting those molecules in RA. This knowledge might provide impetus for developing new therapeutic modalities to treat this chronic disease.

show abstract

“…Interestingly, many genes stimulating the differentiation and functions of osteoclasts were more highly expressed in MoP tissue compared to ARMD. These include C-C motif chemokine ligand 21 (CCL21) [57], triggering receptor expressed on myeloid cells 2 (TREM2) [58] and creatine kinase B (CKB) [59]. Osteoclast-mediated bone resorption is a known feature of adverse reactions seen in MoM [60] and especially in MoP [22] joints, and polyethylene particles have been demonstrated to promote osteoclastic differentiation of mononuclear cells [61].…”

Section: Discussionmentioning

confidence: 99%

Gene expression in adverse reaction to metal debris around metal-on-metal arthroplasty: An RNA-Seq-based study

Pemmari

Leppänen

Paukkeri

et al. 2018

Journal of Trace Elements in Medicine and Biology

View full text Add to dashboard Cite

Joint replacement surgery is a standard treatment of advanced osteoarthritis (OA). Since 2000, cobalt-chromium (CoCr) metal-on-metal (MoM) implants were widely used in hip arthroplasties. Some patients developed "adverse reaction to metal debris" (ARMD) around the prosthesis, resulting in a need for revision surgery. In the present study, we addressed the pathogenesis of ARMD by genome-wide expression analysis. Pseudosynovial ARMD tissue was obtained from revision surgery of Articular Surface Replacement (ASR, DePuy, Warsaw, IN, USA) hip arthroplasties. Control tissue was 1) OA synovium from primary hip arthroplasties and 2) inflammatory pseudosynovial tissue from metal-on-plastic (MoP) implant revisions. In ARMD tissue, the expression of 1446 genes was significantly increased and that of 1881 decreased as compared to OA synovium. Genes associated with immune response, tissue development and certain leukocyte signaling pathways were enriched in the differently (FC > 2) expressed genes. The network analysis proposed PRKACB, CD2, CD52 and CD53 as the central regulators of the greatest (FC > 10) differences. When ARMD tissue was compared to MoP tissue, the expression of 16 genes was significantly higher and that of 21 lower. Many of these genes were associated with redox homeostasis, metal ion binding and transport, macrophage activation and apoptosis. Interestingly, genes central to myofibroblast (AEBP1 and DES) and osteoclast (CCL21, TREM2 and CKB) development were upregulated in the MoP tissue. In network analysis, IL8, NQO1, GSTT1 and HMOX1 were identified as potential central regulators of the changes. In conclusion, excessive amounts of CoCr debris produced by MoM hip implants induces in a group of patients a unique adverse reaction characterized with enhanced expression of genes associated with inflammation, redox homeostasis, metal ion binding and transport, macrophage activation and apoptosis.

show abstract

Stimulation of osteoclast migration and bone resorption by C–C chemokine ligands 19 and 21

Cited by 41 publications

References 49 publications

Profilin 1 Negatively Regulates Osteoclast Migration in Postnatal Skeletal Growth, Remodeling, and Homeostasis in Mice

Profilin 1 Negatively Regulates Osteoclast Migration in Postnatal Skeletal Growth, Remodeling, and Homeostasis in Mice

<p>Role of Chemokines and Chemokine Receptors in Rheumatoid Arthritis</p>

Gene expression in adverse reaction to metal debris around metal-on-metal arthroplasty: An RNA-Seq-based study

Contact Info

Product

Resources

About