| Title |
Attenuation of osteoarthritis via blockade of the SDF-1/CXCR4 signaling pathway
|
|---|---|
| Published in |
Arthritis Research & Therapy, July 2012
|
| DOI | 10.1186/ar3930 |
| Pubmed ID | |
| Authors |
Fangyuan Wei, Douglas C Moore, Yanlin Li, Ge Zhang, Xiaochun Wei, Joseph K Lee, Lei Wei |
| Abstract |
ABSTRACT: INTRODUCTION: This study was performed to evaluate the attenuation of osteoarthritic (OA) pathogenesis via disruption of the stromal cell-derived factor-1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR4) signaling with AMD3100 in a guinea pig OA model. METHODS: OA chondrocytes and cartilage explants were incubated with SDF-1, siRNA CXCR4, or anti-CXCR4 antibody before treatment with SDF-1. Matrix metalloproteases (MMPs) mRNA and protein levels were measured with real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. The 35 9-month-old male Hartley guinea pigs (0.88 kg ± 0.21 kg) were divided into three groups: AMD-treated group (n = 13); OA group (n = 11); and sham group (n = 11). At 3 months after treatment, knee joints, synovial fluid, and serum were collected for histologic and biochemical analysis. The severity of cartilage damage was assessed by using the modified Mankin score. The levels of SDF-1, glycosaminoglycans (GAGs), MMP-1, MMP-13, and interleukin-1 (IL-1β) were quantified with ELISA. RESULTS: SDF-1 infiltrated cartilage and decreased proteoglycan staining. Increased glycosaminoglycans and MMP-13 activity were found in the culture media in response to SDF-1 treatment. Disrupting the interaction between SDF-1 and CXCR4 with siRNA CXCR4 or CXCR4 antibody attenuated the effect of SDF-1. Safranin-O staining revealed less cartilage damage in the AMD3100-treated animals with the lowest Mankin score compared with the control animals. The levels of SDF-1, GAG, MMP1, MMP-13, and IL-1β were much lower in the synovial fluid of the AMD3100 group than in that of control group. CONCLUSIONS: The binding of SDF-1 to CXCR4 induces OA cartilage degeneration. The catabolic processes can be disrupted by pharmacologic blockade of SDF-1/CXCR4 signaling. Together, these findings raise the possibility that disruption of the SDF-1/CXCR4 signaling can be used as a therapeutic approach to attenuate cartilage degeneration. |
X Demographics
The data shown below were collected from the profiles of 5 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 2 | 40% |
| Australia | 1 | 20% |
| United States | 1 | 20% |
| Unknown | 1 | 20% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 4 | 80% |
| Science communicators (journalists, bloggers, editors) | 1 | 20% |
Mendeley readers
The data shown below were compiled from readership statistics for 44 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 2% |
| Spain | 1 | 2% |
| India | 1 | 2% |
| Unknown | 41 | 93% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 10 | 23% |
| Student > Master | 8 | 18% |
| Student > Doctoral Student | 4 | 9% |
| Student > Postgraduate | 3 | 7% |
| Student > Ph. D. Student | 3 | 7% |
| Other | 4 | 9% |
| Unknown | 12 | 27% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 13 | 30% |
| Biochemistry, Genetics and Molecular Biology | 8 | 18% |
| Agricultural and Biological Sciences | 3 | 7% |
| Immunology and Microbiology | 2 | 5% |
| Chemistry | 2 | 5% |
| Other | 4 | 9% |
| Unknown | 12 | 27% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 02 August 2012.
All research outputs
#14,536,679
of 25,374,647 outputs
Outputs from Arthritis Research & Therapy
#2,111
of 3,381 outputs
Outputs of similar age
#99,849
of 178,870 outputs
Outputs of similar age from Arthritis Research & Therapy
#27
of 44 outputs
Altmetric has tracked 25,374,647 research outputs across all sources so far. This one is in the 42nd percentile – i.e., 42% of other outputs scored the same or lower than it.
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We're also able to compare this research output to 44 others from the same source and published within six weeks on either side of this one. This one is in the 38th percentile – i.e., 38% of its contemporaries scored the same or lower than it.