Cytokine-like 1 (CYTL1) Regulates the Chondrogenesis of Mesenchymal Cells

Kim, Jae-Sung; Ryoo, Zae Young; Chun, Jang‐Soo

doi:10.1074/jbc.m700965200

Cited by 63 publications

(105 citation statements)

References 32 publications

(43 reference statements)

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“…Mouse articular cartilage was isolated from femoral heads, femoral condyles, and tibial plateaus from postnatal day 5 mice, as described previously (31). Chondrocytes were maintained as a monolayer in Dulbecco's modified Eagle's medium, and cells on culture day 3 were treated as indicated in each experiment.…”

Section: Methodsmentioning

confidence: 99%

Dkk‐1 expression in chondrocytes inhibits experimental osteoarthritic cartilage destruction in mice

Oh¹,

Chun²,

Chun³

2012

Arthritis & Rheumatism

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106

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Objective. Dkk is a family of canonical Wnt antagonists with 4 members (Dkk-1, Dkk-2, Dkk-3, and Dkk-4). We undertook this study to explore the roles of Dkk-1 and Dkk-2 in osteoarthritic (OA) cartilage destruction in mice.Methods. Expression of Dkk and other catabolic factors was determined at the messenger RNA and protein levels in human and mouse OA cartilage. Experimental OA in mice was induced by destabilization of the medial meniscus (DMM) or by intraarticular injection of Epas1 adenovirus (AdEPAS-1). The role of Dkk in OA pathogenesis was examined by intraarticular injection of AdDkk-1 or by using chondrocyte-specific Dkk1 (Col2a1-Dkk1)-transgenic mice and Dkk2 (Col2a1-Dkk2)-transgenic mice. Primary culture mouse chondrocytes were also treated with recombinant Dkk proteins.Results. We found opposite patterns of Dkk1 and Dkk2 expression in human and mouse experimental OA cartilage: Dkk1 was up-regulated and Dkk2 was downregulated. Overexpression of Dkk1 by intraarticular injection of AdDkk-1 significantly inhibited DMMinduced experimental OA. DMM-induced OA was also significantly inhibited in Col2a1-Dkk1-transgenic mice compared with their wild-type littermates. However, Col2a1-Dkk2-transgenic mice showed no significant difference in OA pathogenesis. Wnt-3a, which activates the canonical Wnt pathway, induced Mmp13 and Adamts4 expression in primary culture chondrocytes, an effect that was significantly inhibited by Dkk-1 pretreatment or Dkk1 overexpression.Conclusion. Our findings indicate that expression of Dkk1, but not Dkk2, in chondrocytes inhibits OA cartilage destruction. The protective effect of Dkk-1 appears to be associated with its capacity to inhibit Wnt-mediated expression of catabolic factors, such as Mmp13, providing evidence that Dkk-1 might serve as a therapeutic target for OA treatment.

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Section: Methodsmentioning

confidence: 99%

Dkk‐1 expression in chondrocytes inhibits experimental osteoarthritic cartilage destruction in mice

Oh¹,

Chun²,

Chun³

2012

Arthritis & Rheumatism

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106

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“…(18) Detailed protocols are listed in the Supplemental Materials and Methods. Cells were maintained in the absence or presence of various reagents, including insulinlike growth factor-1, lentivirus containing Dkk1 or Dkk2, and recombinant Dkk1 or Dkk2 protein (R&D System, Minneapolis, MN, USA) as indicated in the text.…”

Section: Animalsmentioning

confidence: 99%

“…Hypertrophic maturation was determined by examining the expression of matrix metalloproteinase (Mmp) 13 using RT-PCR and by detecting mineralization using alizarin red staining. (18) PCR primers and conditions are shown in Supplemental Table 1. Cartilage and skeletal staining, histological analysis, immunohistochemistry, and immunofluorescence microscopy Cartilage and skeletons of whole-mouse embryos or postnatal mice, and mineralized zones in developing bone were stained with alcian blue, alizarin red, and von Kossa. (19) The lengths of bone and mineralized zones were measured using the AxioVision microscope image analysis program (Carl Zeiss, Jena, Germany).…”

Section: Animalsmentioning

confidence: 99%

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Misexpression of Dickkopf-1 in endothelial cells, but not in chondrocytes or hypertrophic chondrocytes, causes defects in endochondral ossification

Oh¹,

Ryu²,

Jeon³

et al. 2012

Journal of Bone and Mineral Research

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Developing cartilage serves as a template for long-bone development during endochondral ossification. Although the coupling of cartilage and bone development with angiogenesis is an important regulatory step for endochondral ossification, the molecular mechanisms are poorly understood. One possible mechanism involves the action of Dickkopf (DKK), which is a family of soluble canonical Wnt antagonists with four members (DKK1-4). We initially observed opposite expression patterns of Dkk1 and Dkk2 during angiogenesis and chondrocyte differentiation: downregulation of Dkk1 and upregulation of Dkk2. We examined the in vivo role of Dkk1 and Dkk2 in linking cartilage/bone development and angiogenesis by generating transgenic (TG) mice that specifically express Dkk1 or Dkk2 in chondrocytes, hypertrophic chondrocytes, or endothelial cells. Despite specific expression pattern during cartilage development, chondrocyte-and hypertrophic chondrocyte-specific Dkk1 and Dkk2 TG mice showed normal developmental phenotypes. However, Dkk1 misexpression in endothelial cells resulted in defects of endochondral ossification and reduced skeletal size. The defects are caused by the inhibition of angiogenesis in developing bone and subsequent inhibition of apoptosis of hypertrophic chondrocytes and cartilage resorption. ß

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“…Chun and colleagues (10,11) determined that Cytl1 2/2 mice were more sensitive to osteoarthritic cartilage destruction. Chao et al (12) demonstrated that CYTL1 could significantly prevent inflammatory arthritis.…”

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confidence: 99%

Cytokine-like 1 Chemoattracts Monocytes/Macrophages via CCR2

Wang

et al. 2016

The Journal of Immunology

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Cytokine-like 1 (CYTL1) is a novel potential cytokine that was first identified in CD34+ cells derived from bone marrow and cord blood, and it was also found using our immunogenomics strategy. The immunobiological functions of CYTL1 remain largely unknown, and its potential receptor(s) has not been identified. A previous proposed hypothesis suggested that CYTL1 had structural similarities with CCL2 and that CCR2 was a potential receptor of CYTL1. In this study, we verify that CYTL1 possesses chemotactic activity and demonstrate that its functional receptor is CCR2B using a series of experiments performed in HEK293 cells expressing CCR2B or CCR2B-EGFP, including chemotaxis, receptor internalization, and radioactive binding assays. CYTL1 chemoattracts human monocytes but not PBLs, and its chemotactic activity toward monocytes is dependent on the CCR2B-ERK pathway. Furthermore, both human and mouse recombinant CYTL1 protein have chemotactic effects on macrophages from wild-type mice but not from Ccr2−/− mice. Furthermore, the chemotactic activity of CYTL1 is sensitive to pertussis toxin. All of the above data confirm that CCR2B is a functional receptor of CYTL1.

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Cytokine-like 1 (CYTL1) Regulates the Chondrogenesis of Mesenchymal Cells

Cited by 63 publications

References 32 publications

Dkk‐1 expression in chondrocytes inhibits experimental osteoarthritic cartilage destruction in mice

Dkk‐1 expression in chondrocytes inhibits experimental osteoarthritic cartilage destruction in mice

Misexpression of Dickkopf-1 in endothelial cells, but not in chondrocytes or hypertrophic chondrocytes, causes defects in endochondral ossification

Cytokine-like 1 Chemoattracts Monocytes/Macrophages via CCR2

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