16 research outputs found
Anatomic Parameters of the Lisfranc Joint Complex in a Radiographic and Cadaveric Comparison
Chondroprotective Effects and Mechanisms of Dextromethorphan: Repurposing Antitussive Medication for Osteoarthritis Treatment
Osteoarthritis (OA) is the most common joint disorder and primarily affects older people. The ideal anti-OA drug should have a modest anti-inflammatory effect and only limited or no toxicity for long-term use. Because the antitussive medication dextromethorphan (DXM) is protective in atherosclerosis and neurological diseases, two common disorders in aged people, we examined whether DXM can be protective in pro-inflammatory cytokine-stimulated chondrocytes and in a collagen-induced arthritis (CIA) animal model in this study. Chondrocytes were prepared from cartilage specimens taken from pigs or OA patients. Western blotting, quantitative PCR, and immunohistochemistry were adopted to measure the expression of collagen II (Col II) and matrix metalloproteinases (MMP). DXM significantly restored tumor necrosis factor-alpha (TNF-α)-mediated reduction of collagen II and decreased TNF-α-induced MMP-13 production. To inhibit the synthesis of MMP-13, DXM blocked TNF-α downstream signaling, including I kappa B kinase (IKK)α/β-IκBα-nuclear factor-kappaB (NF-κB) and c-Jun N-terminal kinase (JNK)-activator protein-1 (AP-1) activation. Besides this, DXM protected the CIA mice from severe inflammation and cartilage destruction. DXM seemed to protect cartilage from inflammation-mediated matrix degradation, which is an irreversible status in the disease progression of osteoarthritis. The results suggested that testing DXM as an osteoarthritis therapeutic should be a focus in further research
Chondroprotective Effects and Mechanisms of Dextromethorphan: Repurposing Antitussive Medication for Osteoarthritis Treatment
A New Application of Parallel Synthesis Strategy for Discovery of Amide-Linked Small Molecules as Potent Chondroprotective Agents in TNF-α-Stimulated Chondrocytes.
As part of an effort to profile potential therapeutics for the treatment of inflammation-related diseases, a diversity of amide-linked small molecules was synthesized by using parallel synthesis strategy. Moreover, these new compounds were also evaluated for their inhibitory effects on nitric oxide (NO) by using tumor necrosis factor alpha (TNF-α)-induced inflammatory responses in chondrocytes. Among the tested compounds, N-(3-chloro-4-fluorophenyl)-2-hydroxybenzamide (HS-Ck) was the most potent inhibitor of NO production and inducible nitric oxide synthase (iNOS) expression in TNF-α-stimulated chondrocytes. In addition, our biological results indicated that HS-Ck might suppress the expression levels of iNOS and matrix metalloproteinases-13 (MMP-13) activities through downregulating the activation of nuclear factor kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT-3) transcriptional factors. Therefore, the parallel synthesis was successful used to develop a new class of potential anti-inflammatory agents as chondroprotective candidates for the treatment of osteoarthritis
Combined Innovative Portal Arthroscopy and Fluoroscopy-Assisted Reduction and Fixation in Subtle Injury of the Lisfranc Joint Complex: Analysis of 10 Cases
Effects of HS-Ck on the expression levels of MMP-13 in TNF-α-induced porcine chondrocytes.
<p>(A) Porcine chondrocytes were pretreated with various doses of HS-Ck or the DMSO solvent as vehicle (V) control for 2 h and then stimulated with TNF-α (5 ng/mL) for 24 h. The activities of pro-MMP-13 released into the culture supernatants were determined by using Western Blotting assay. (B) The expression levels of pro-MMP-13 activities were expressed as the relative band intensity. The representative data out of at least three independent experiments are shown. *<i>P</i> < 0.05 compared to the TNF-α-stimulated in the absence of HS-Ck treatment.</p
Effects of HS-Ck on TNF-α-induced NO production and cell viability in porcine chondrocytes.
<p>(A) Porcine chondrocytes were pretreated with various doses of HS-Ck or the DMSO solvent as vehicle (V) control for 2 h and then stimulated with TNF-α for 24 h. The production of NO was determined by using the Griess reagent. (B) To determine potential cytotoxic effects of HS-Ck, porcine chondrocytes were treated with various concentrations of HS-Ck for 24 h. The cells and culture supernatants were collected and determined by using MTT assay. The representative data out of at least three independent experiments are shown. *<i>P</i> < 0.05 compared to the TNF-α-stimulated in the absence of HS-Ck treatment.</p
Effects of HS-Ck on TNF-α-stimulated activation of NF-κB and STAT-3 transcriptional factors in porcine chondrocytes.
<p>For determining the effects of HS-Ck on TNF-α-induced DNA-binding activity of NF-κB (A) and STAT-3 (B), various doses of HS-Ck were pretreated with nuclear extracts for 30 min before the addition of radiolabeled oligonucleotides. The effects of HS-Ck on TNF-α-induced DNA-binding activity of NF-κB and STAT-3 were determined by using EMSA. The expression levels of NF-κB (A) and STAT-3 (B) were expressed as the relative band intensity. DMSO solvent was showed as vehicle (V) control. The representative data out of at least three independent experiments are shown. **<i>P</i> < 0.01 compared to the TNF-α-stimulated in the absence of HS-Ck treatment.</p
Two potent amide-linked small molecules (HS-Cf and HS-Cm) were identified their biological activities in our previous studies.
<p>Two potent amide-linked small molecules (HS-Cf and HS-Cm) were identified their biological activities in our previous studies.</p