| 1. |
- Deng, Huan, et al.
(författare)
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Altered Expression of the Hedgehog Pathway Proteins BMP2, BMP4, SHH, and IHH Involved in Knee Cartilage Damage of Patients With Osteoarthritis and Kashin-Beck Disease
- 2022
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Ingår i: Cartilage. - : Sage Publications. - 1947-6035 .- 1947-6043. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the expression of Hedgehog (HH) signaling pathway proteins in knee articular cartilage from Kashin-Beck disease (KBD) and osteoarthritis (OA) patients.METHODS: Knee articular cartilage samples were collected from normal (N), OA, and KBD adults (aged 38-60 years) and divided into 3 groups with 6 subjects in each group. The localization of the HH pathway proteins bone morphogenetic protein 2 (BMP2), bone morphogenetic protein 4 (BMP4), Sonic hedgehog (SHH), and Indian hedgehog (IHH) was observed with the microscope after immunohistochemical (IHC) staining. Positive staining cell rates of each proteins were compared.RESULTS: The strongest stainings of all proteins were observed in the middle zones of all 3 groups. The positive staining rates of BMP4 and IHH were significantly lower in the OA and KBD groups than those in the N group in all 3 zones. The positive staining rates of BMP2 and SHH tend to be lower in the OA and KBD groups than those in the N group in the deep zone, while higher in the OA and KBD groups than those in the N group in superficial and middle zones.CONCLUSIONS: Altered expression of the HH pathway proteins BMP2, BMP4, SHH, and IHH was found in OA and KBD articular cartilage. There seemed to be a compensatory effect between SHH and IHH in cartilage damage. Further studies on the pathogenesis of OA and KBD may be carried out from these aspects in the future.
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| 2. |
- Lei, Jian, et al.
(författare)
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Altered expression of aggrecan, FAM20B, B3GALT6, and EXTL2 in patients with osteoarthritis and Kashin-Beck disease
- 2021
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Ingår i: Cartilage. - : Sage Publications. - 1947-6035 .- 1947-6043. ; 13:Suppl 1, s. 818S-828S
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The objective of this study was to investigate the expression of enzymes involved in synthesis and modification of chondroitin sulfate (CS) in knee cartilage tissue of patients with osteoarthritis (OA) and Kashin-Beck disease (KBD).METHODS: The knee articular cartilage samples were obtained from 18 age- and gender-matched donors with 6 each in KBD, OA, and control groups. Hematoxylin and eosin (HE) staining, toluidine blue (TB) staining, and immunohistochemical (IHC) staining were performed to estimate the expression level and localization of aggrecan, along with FAM20B, GalT-II, and EXTL2, which are associated with CS synthesis and modification. Rank-based analyses of variance test was used for the multiple comparisons of discrepancy in the positive staining rate among the 3 groups.RESULTS: In HE and TB staining results, damaged morphology, decreased chondrocyte numbers and proteoglycans were observed in OA and KBD groups compared with the control group. In line with these trends, the positive staining rates of aggrecan were lower in KBD and OA groups than in the control group. Meanwhile, the positive staining rates of CS chain modifying enzymes FAM20B, GalT-II, and EXTL2 decreased in OA and KBD groups.CONCLUSIONS: In conclusion, it was demonstrated that altered expression of CS chain modifying enzymes in OA and KBD groups influenced the synthesis procession of CS and could contribute to the damage of cartilage. Further investigation of these enzymes can provide new theoretical and experimental targets for OA and KBD pathogenesis studies.
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| 3. |
- Lei, Jian, et al.
(författare)
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Proteomic analysis of knee cartilage reveals potential signaling pathways in pathological mechanism of Kashin-Beck disease compared with osteoarthritis
- 2020
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- The pathological mechanism of Kashin-Beck disease (KBD), an endemic osteoarthritic disease, remains to be poorly understood. This study was designed to identify signaling pathways and crucial proteins involved in the pathological mechanism of KBD compared with osteoarthritis (OA). The knee cartilage samples were collected from gender- and age-matched KBD (n = 9) and OA (n = 9) patients. After pre-processing, samples were labeled with Tamdem Mass Tags 6plex multiplex kit, and analyzed by liquid chromatography-tandem mass spectrometry. Proteomic results were analyzed with gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interactions (PPI). The differential abundance proteins from KBD and OA were validated using western blot analysis. As a result, A total number of 375 proteins were identified to have differential abundance between KBD and OA, of which 121 and 254 proteins were observed to be up-regulated or down-regulated in KBD group. GO analysis shows that the differential abundant proteins are associated with cell junction and signal transducer activity from extracellular to intracellular. KEGG pathways enrichment and PPI network indicate four major pathways, including extracellular matrix -receptor interaction, focal adhesion, phosphatidylinositol 3-kinase (PI3K)-Protein kinase B (Akt), and Ras signaling pathways were involved in the degeneration of cartilage. Moreover, integrins, laminins, NF-κB and other regulative molecules were found as crucial proteins. In conclusion, our results demonstrated that compared with OA, the differential abundance proteins and signaling pathways may contribute to the occurrence and development of joint damage in KBD. Further investigation of their regulative roles and interaction may provide new insights into the pathological mechanisms and therapeutic targets for KBD.
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| 4. |
- Xiao, Xiang, et al.
(författare)
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Chondroitin Sulfate and Hyaluronic Acid Perfusion for Interstitial Cystitis/Bladder Pain Syndrome : A Systematic Review and Meta-Analysis
- 2021
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Ingår i: Science Insights. - : Insights Publisher. - 2372-8191 .- 2329-5856. ; 39:4, s. 361-373
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Forskningsöversikt (refereegranskat)abstract
- Currently, no suitable delivery methods are available for the drugs to interstitial cystitis/ bladder pain syndrome (IC/BPS). Herein we systematically evaluated the therapeutic effects of intravesical infusion of hyaluronic acid (HA) and chondroitin sulfate (CS) in patients with IC/BPS. This study includes randomized controlled trials (RCT) and self-controlled studies of IC/BPS patients treated with HA, CS, or both. English databases like PubMed, Cochrane Library, Embase, and Medline were searched until up to January 31, 2021. Information was extracted based on the inclusion and exclusion criteria, and then meta-analysis was performed. Sixteen studies including 491 patients were included and analyzed. The responsive rate of treatment was 91.24%. In 3 RCTs, the analogue scale (VAS) for pain on fix-effect model was [mean difference, MD -0.57 (95%CI, -1.55, -0.41)]. A significant improvement on random-effect model was [MD -2.78 (95%CI, -3.48, -2.07)] in 13 self-controlled studies. Outcomes on O’Leary-Sant Interstitial Cystitis Symptom Index, Problem Index, frequency, urgency, and bladder capacity were also significantly improved. Subgroup analysis showed significant difference between HA, CS, and the combination, and the perfusion of HA was more effective (Z = 29.97, P < 0.01). Also, different follow-up times after last treatment showed significant difference (Z = 7.69, P < 0.01). It can be beneficial for IC/BPS patients who have not responded to conventional treatments.
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