CELLULAR SIGNALLING
·
2025
·
IF 3.7
Yuyan Sun,Ziyu Luo,Haiqi Zhou,Sha Wu,Hongwei Shen,Yuanyuan Fu,Thai Namanh Ngo,Wen Wang,Yuanrong Wang,Ying Kong
Chondrocyte mechanotransduction dysfunction is a key feature of osteoarthritis (OA). Previous studies have demonstrated that primary cilia play a crucial role in chondrocyte mechanosensation and signal transduction. Transient Receptor Potential Vanilloid 4(TRPV4), which is highly expressed on primary cilia, is a critical mechanotransduction protein and one of the most important Ca 2+ channels. However, the interplay between the mechanism of primary cilia-mediated signaling and that of TRPV4 channel regulation remains poorly understood. Here, we demonstrate that OA chondrocytes and Intraflagellar Transport Protein 88(Ift88) conditional knockout (cKO) mice exhibit reduced ciliary incidence. This results in cartilage degeneration. TRPV4 expression inversely correlated with ciliary integrity, increasing as cilia were lost. In cilia-intact healthy chondrocytes, TRPV4 antagonism inhibited Ca 2+ -dependent NF-κB activation while promoting type II collagen(COL2) synthesis. These effects were abolished by Interleukin-1 beta(IL-1β)-induced ciliary defect or IFT88 deficiency. Chromatin immunoprecipitation(ChIP) analysis revealed disrupted p65 binding to the COL2 promoter upon the loss of ciliary integrity. Crucially, Ift88 cKO chondrocytes showed unresponsive of the TRPV4 channel, as confirmed by Ca 2+ flux and changes in the expression levels of NF-κB and COL2. Our findings position primary cilia as indispensable regulators of TRPV4-mediated NF-κB - COL2 signaling, offering mechanistic insights into OA pathogenesis and identifying IFT88 as a therapeutic checkpoint.
研究领域:
分子生物学
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细胞生物学
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骨关节炎病理学
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信号转导
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转化医学
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软骨生物学
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机械生物学
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产品关联
DOI
PubMed
高影响因子
FOOD HYDROCOLLOIDS
·
2024
·
IF 11
Rong Xu,Yue Gu,Lin Zheng,Mingtao Huang,Mouming Zhao
Previously, we presented a green and efficient separation method for soluble undenatured type II collagen (SC II) based on the complex coacervation of SC II and anionic polysaccharides , and demonstrated the significant impact of molecular weight (M w ). In this study, we combined differential scanning calorimetry (DSC), microscale thermophoresis (MST) and molecular dynamics simulation (MDS) to further explore the affinity and interaction types of SC II with different anionic polysaccharides . Results showed that the denaturation temperature of SC II increased (about 3 °C) after complex coacervating with chondroitin sulfate (CS, a small anionic polysaccharide), which might be related to their strong affinity (dissociation constant of K d and binding energy were about 3.04 × 10 −6 mg/mL and −4054.97 kJ/mol, respectively), and the molecular weight of anionic polysaccharides had a greater impact than chain conformation. The non-covalent interactions between SC II and anionic polysaccharides were mainly hydrogen bonds, followed by hydrophobic interactions and ionic bonds. The hydroxyl and sulfate groups in polysaccharides could form extensive hydrogen bonds and small amount of ionic bonds with a large number of amino acids in SC II, and the hydrophobic groups such as methyl also formed hydrophobic interactions with hydrophobic parts in SC II (such as Pro82, Pro85, Val88). Importantly, the smaller the M w of anionic polysaccharides, the faster they formed stable interactions with SC II. Therefore, anionic polysaccharides with smaller M w had higher affinity and faster non-covalent interactions formation speed with SC II, resulting in more compact structure and higher thermal stability of the complexes.
研究领域:
生物化学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
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2020
·
IF 2.69
Weiwei Lan,Mengjie Xu,Xiumei Zhang,Liqin Zhao,Di Huang,Xiaochun Wei,Weiyi Chen
Type II collagen (Col-II) is one of the important organic components of the cartilage extracellular matrix (ECM). Such natural material is known for its good biocompatibility, but it could not provide a good supporting environment for seed cells due to its rapid degradation and poor strength. In the present work, different contents of Col-II were incorporated into porous polyvinyl alcohol (PVA) to fabricate porous PVA/Col-II composite hydrogels for cartilage tissue engineering. The results illustrate that, after incorporation of Col-II, the elasticity modulus of the composite hydrogels firstly increases, and then decreases (under moisture state). The elasticity modulus of PVA/Col-II (at the ratio of 1:1) hydrogels reaches 11 ± 1.7 KPa, about two-fold higher than pure PVA hydrogels (4.9 ± 0.6 KPa). Meanwhile, all hydrogels exhibit relatively high water content (> 95%) and porosity (> 75%). The degradation analysis indicates that Col-II incorporation induce a high degradation ratio of the composite hydrogels. Cell culture results show PVA/Col-II hydrogels have no negative effects on cells viability and proliferation. The PVA/Col-II hydrogels may possess a potential application in the field of articular cartilage tissue engineering and regeneration.
研究领域:
生物材料学
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组织工程学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Pharmacognosy Magazine
·
2025
·
IF 0.9
Yezhou Li,Chengjian Tang
Background and PurposeAlginate and gelatin have biocompatibility and biodegradability for drug formulations or carriers, but the roles and mechanisms in cartilage injury (CI) repair remain unclear. This research investigated the application of alginate-collagen hydrogel (ACH) in rat CI repair and its related mechanisms through in vitro and in vivo experiments.Materials and MethodsAlginate and modified collagen solutions were mixed to prepare the ACH. The obtained samples were characterized, and their sustained release properties were determined. L929 mouse fibroblasts were assigned into a blank control group (BC group, untreated), a positive control group (PC group, treated with 6.4% phenol), a negative control group (NC group, treated with tissue culture polystyrene), and an ACH group (treated with ACH). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay assessed cell viability. Meanwhile, the cytotoxicity of the ACH and its impact on cell proliferation and cell attachment capabilities were analyzed. Thirty 4-week-old specific pathogen-free Sprague-Dawley rats were randomly grouped into a chondrocyte group (chondrocytes collected and cultured), a cPAGE group (chondrocytes treated with ACH), a model group (CI model), and an mPAGE group (CI model treated with ACH). The influence of ACH on chondrocyte proliferation and type II collagen (COL-II) expression were assessed via cell counting kit 8 (CCK-8) assay and immunofluorescence staining. Furthermore, the impacts of ACH on chondrocyte tissue and COL-II expression were analyzed using Safranin O-Fast Green staining, the International Cartilage Repair Society (ICRS) score, and COL-II tissue staining. Immunoblotting was utilized to detect tumor necrosis factor alpha (TNF-α), nuclear factor kappa-B (NF-κB), matrix metalloproteinase 13 (MMP-13), and COL-II proteins in cartilage tissue.ResultsThe release rate of the constructed ACH reached over 85% within 72 h and achieved degradation equilibrium within 5 days with a weight loss rate of over 60%. L929 fibroblast culture results showed that the ACH posed no significant cytotoxicity, and cell attachment results were not obviously different from those on tissue culture plates (p < .05). MTT assay results demonstrated that the ACH exerted no adverse effects on L929 cell proliferation and growth, indicating good biocompatibility. CCK-8 and COL-II results indicated that chondrocyte proliferation in the cPAGE group was markedly higher versus that in the chondrocyte group (p < .05). Besides, animal experiments unveiled that, relative to the CI group, the mPAGE group had more chondrocytes, upregulated COL-II, and higher ICRS scores (p < .05). MMP-13, NF-κB, and TNF-α were downregulated, and COL-II was upshifted in the mPAGE group, with remarkable differences (p < .05).ConclusionACH exhibited excellent biocompatibility and low cytotoxicity, promoted cell proliferation and growth, and facilitated chondrocyte proliferation in rat CI repair, offering a valuable research foundation for CI treatment.
研究领域:
生物材料学
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组织工程学
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医学
✓ 已验证
DOI
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2018
·
IF 3.457
Qinran Sun,Fangming Liu,Min Gao,Wenqing Wu,Weiju Liu,Cong Yin,Zhongshu Zhu,Lijin Zhang,Xiufang Ding,Yanping Guo,Hui Gong,Xuguo Sun,Daoping Zhang
Cervical spondylosis (CS), which is resulted from degeneration of cervical intervertebral disc, is a common disease seriously threatening human health and quality of life. However, there is still no effective clinic strategies for the treatment of this disease. The acupoint stimulation with needle-scalpel is a widely used approach to treat orthopedic diseases. In the present study, we evaluated the therapeutic effects of acupoint stimulation around neck with needle-scalpel on delaying the degeneration of cervical intervertebral discs and hopefully provided an approach for the precaution and early intervention of CS. We firstly established a rat model of CS by cervical static-dynamic imbalance to mimics disc degeneration and then stimulated the acupoints around neck with needle-scalpel. The cervical intervertebral disc samples were collected to measure type I and II collagen by quantitative PCR (qPCR), immunohistochemistry, and western blot. The changes in micro-structure and ultra-structure of nucleus pulposus were analyzed under the optical microscope and electron microscope respectively. Acupoint stimulation with needle-scapelon increased type I collagen production and decreased type II collagen production, and improved the micro-structure and ultra-structure of nucleus pulposus. Our results suggest that acupoint stimulation around neck with needle-scapelon could inhibit intervertebral disc degeneration through modulating the extracellular matrix collagen system and improving the changed structure of nucleus pulposus.
研究领域:
骨科
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中医
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生物医学研究
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DOI
PubMed
高影响因子
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
·
2018
·Vol. 106
·期 5
·1258-1268
·
IF 3.231
Xiaopeng Zhou,Yiqing Tao,Erman Chen,Jingkai Wang,Weijing Fang,Tengfei Zhao,Chengzhen Liang,Fangcai Li,Qixin Chen
Adipose-derived stem cells (ADSCs)-based tissue engineering was a promising method to treat intervertebral disc degeneration. Type II collagen is a native component in the nucleus pulposus (NP), and has the ability to promote ADSCs to differentiate into NP-like cells. In this article, we aimed to establish a genipin-cross-linked three-dimensional (3D) type II collagen scaffold, and determine the biological effects of the scaffold on ADSCs differentiating into a NP-like phenotype. Different concentrations of genipin were used to cross-link the 3D type II collagen scaffold. Microstructure, surface topography, mechanical strength, porosity, swelling property, and biological stability of the scaffolds were detected to evaluate the scaffold properties. Cell proliferation, gene and protein expression were measured to access the biological effects of the scaffolds on ADSCs, and the related molecular mechanism was investigated. Cross-linking by genipin increased the stability of the type II collagen scaffolds, but deformed the configuration of scaffolds and changed the intrinsic properties of type II collagen. scaffold cross-linked with 0.1% genipin improved the biostability on the basis of maintaining the configuration of scaffold. In addition, the 0.1% genipin-cross-linked scaffold promoted ADSCs proliferation and differentiation into NP-like cells, along with the increasing gene and protein expressions of Sonic Hedgehog (Shh). All these results suggested that 0.1% genipin was the optimal concentration to establish a bio-stable 3D type II collagen scaffold, which inducing ADSC proliferation and differentiation toward a NP-like phenotype through the activation of Shh signaling pathway. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1258–1268, 2018.
研究领域:
组织工程
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干细胞生物学
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骨科
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2021
·
IF 9.381
Zhengwei Liu,Xiaoqiong Mo,Fenbo Ma,Sijing Li,Guofeng Wu,Bin Tang,Lijun Lin
Osteoarthritis (OA) is an age-related joint disorder and one of the leading causes of physical disability. In this study, we designed and synthesized a new polysaccharide complex, carboxymethyl chitosan strontium (CMCS-Sr), which is believed to have positive effects on relieving OA. The synthesized CMCS-Sr was structurally verified by SEM, EDS, FTIR, etc. The therapeutic effects of CMCS-Sr were evaluated using various biological experiments. The cell viability and apoptosis results reveal that CMCS-Sr can significantly promote the proliferation and suppress OA chondrocytes apoptosis in vitro . The immunofluorescence staining results suggest that CMCS-Sr facilitates the promotion of the secretion of Type II collagen (Col-II). The transcriptomic results support the observed positive effects of CMCS-Sr on inhibiting chondrocytes apoptosis and alleviating inflammatory reactions. Moreover, animal study demonstrates that CMCS-Sr effectively reduced articular cartilage damage and subchondral bone degradation. Therefore, we propose the use of CMCS-Sr as a promising candidate for relieving OA.
研究领域:
药理学
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骨科
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Yuan Wang,Jinfang Liu,Like Mao,Fang Yuan,Yanxiang Gao
In this study, the structural design and physicochemical property enhancement of undenatured type II collagen (UC-II) nanofibrils with sodium alginate (SA) coating induced by calcium ions (Ca 2+ ) were investigated. The research aimed to elucidate the impact of Ca 2+ concentration on the morphology, thermal stability , and digestive resistance, as well as to assess the potential of UC-II/SA nanofibrils as a delivery system for curcumin (Cur). A series of Ca 2+ concentrations (1–9 mM) were methodically applied to optimize the condition that maintains the triple-helical structure of UC-II, thereby enhancing its functional properties. It was found that the Ca 2+ level up to 5 mM effectively preserved the structural integrity and improved thermal stability of UC-II, with the added benefit of ensuring the substantial delivery of active fragment to small intestine (70.7 %), which was 3.43 times greater than that of uncoated UC-II. Moreover, incorporating Cur into the UC-II/SA nanofibrils resulted in a 300 times increase in Cur solubility and showcased the superior dispersion stability, antioxidant activity , and sustained release profile during simulated digestion. These findings underscored the dual functionality of the UC-II/SA system as both a stabilizing agent for UC-II nanofibrils and an efficient carrier for Cur delivery.
研究领域:
材料科学
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药学
·
纳米技术
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CYTOTECHNOLOGY
·
2021
·Vol. 73
·期 5
·715-726
·
IF 2.058
Xu Haiqiao,Lin Shibang,Huang Haizhou
CCL22, which could induce chondrocyte apoptosis, was identified to be overexpressed in damaged cartilage. This study was conducted with the aim of investigating the effects of CCL22 interference on chondrocyte injury. The osteoarthritis model was established by stimulating chondrocytes with LPS. The expressions of CCL22, CCR4, matrix metallopeptidase (MMP) 3, MMP9, MMP13, (a disintegrin and metalloproteinase with thrombospondin-like motifs) ADAMTS-4, collagen II and inflammatory cytokines were measured using quantitative reverse transcription PCR (RT-qPCR) and western blot. Besides, immunoprecipitation (IP) was employed to verify the binding of CCL22 and CCR4. After CCR4 was overexpressed, cell viability was observed using Cell Counting Kit-8 (CCK-8). Additionally, cell apoptosis as well as its related proteins was detected by TUNEL and western blot, respectively. ng What’s more, glycosaminoglycan (GAG) level was detected using GAG kits. CCL22 and CCR4 expression increased noticeably in LPS-stimulated ATDC5 chondrocytes. CCL22 inhibition could suppress the expression of CCR4 in LPS-induced ATDC5 cells. Likewise, CCL22 inhibition could revive the activation of LPS-induced ATDC5 cells by regulating CCR4. In addition, CCL22 knockdown alleviated inflammatory response and cell apoptosis through CCR4. Furthermore, the cartilage degradation of ADTC5 cells could be relieved by CCL22 silence via regulating CCR4. CCL22/CCR4 expression was increased in osteoarthritic cartilage injury and participated in the inflammation and cartilage degradation of chondrocytes.
研究领域:
风湿病学
·
细胞生物学
·
分子生物学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2025
·
IF 14.6
Wenxiang Hong,Hongbo Ma,Zhaoxu Yang,Jiaying Wang,Bowen Peng,Longling Wang,Yiwen Du,Lijun Yang,Lijiang Zhang,Zhibin Li,Han Huang,Difeng Zhu,Bo Yang,Qiaojun He,Jiajia Wang,Qinjie Weng
Dendritic cells (DCs) serve as the primary antigen-presenting cells in autoimmune diseases, like rheumatoid arthritis (RA), and exhibit distinct signaling profiles due to antigenic diversity. Type II collagen (CII) has been recognized as an RA-specific antigen; however, little is known about CII-stimulated DCs, limiting the development of RA-specific therapeutic interventions. In this study, we show that CII-stimulated DCs display a preferential gene expression profile associated with migration, offering a new perspective for targeting DC migration in RA treatment. Then, saikosaponin D (SSD) was identified as a compound capable of blocking CII-induced DC migration and effectively ameliorating arthritis. Optineurin (OPTN) is further revealed as a potential SSD target, with Optn deletion impairing CII-pulsed DC migration without affecting maturation. Function analyses uncover that OPTN prevents the proteasomal transport and ubiquitin-dependent degradation of C–C chemokine receptor 7 (CCR7), a pivotal chemokine receptor in DC migration. Optn -deficient DCs exhibit reduced CCR7 expression, leading to slower migration in CII-surrounded environment, thus alleviating arthritis progression. Our findings underscore the significance of antigen-specific DC activation in RA and suggest OPTN is a crucial regulator of CII-specific DC migration. OPTN emerges as a promising drug target for RA, potentially offering significant value for the therapeutic management of RA.
研究领域:
免疫学
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风湿病学
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药理学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2021
·
IF 9.381
Kai Ren,Xiang Ke,Zhu Chen,Yao Zhao,Lu He,Peng Yu,Jiaqi Xing,Jun Luo,Jing Xie,Jianshu Li
High friction of damaged cartilage requires long-acting lubricated additive, which can also effectively scavenge reactive oxidative species (ROS) produced by mechanically stimulated chondrocytes . In this study, xanthan gum (XG) was grafted by poly (sulfobetaine methacrylate) (PSBMA) (the [XG]/[SBMA] molar ratio is 1:5 or 1:10), forming nanoparticles and then conjugated with collagen II-binding peptide, finally obtaining CBPXGSB1/5 or CBPXGSB1/10. Therein, the CBPXGSB1/5 was chosen as optimal lubricated additive. The results show that hydrated effect of PSBMA side chains endows CBPXGSB1/5 with favorable lubrication property (COF is 0.063). Furthermore, the CBPXGSB1/5 combining lubrication property and specific binding capability together may achieve the long-acting lubrication for injured cartilage in medical field. The CBPXGSB1/5 also possesses antioxidation verified by DPPH assay and exhibits synergistically enhanced ROS ( OH, O 2 − and H 2 O 2 ) scavenging. Besides, cytotoxicity experiment demonstrates that CBPXGSB1/5 has good biocompatibility. Therefore, multifunctional CBPXGSB1/5 developed here may have promising application potential in osteoarthritis treatment.
研究领域:
材料科学
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生物医学工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2018
·
IF 6.383
Xiaopeng Zhou,Jingkai Wang,Weijing Fang,Yiqing Tao,Tengfei Zhao,Kaishun Xia,Chengzhen Liang,Jianming Hua,Fangcai Li,Qixin Chen
Nucleus pulposus (NP) degeneration is usually the origin of intervertebral disc degeneration and consequent lower back pain. Although adipose-derived stem cell (ADSC)-based therapy is regarded to be promising for the treatment of degenerated NP, there is a lack of viable cell carriers to transplant ADSCs into the NP while maintaining cell function. In this study, we developed a type II collagen/chondroitin sulfate (CS) composite hydrogel-like ADSC (CCSA) delivery system with genipin as the cross-linking agent. The induction effect of the scaffold on ADSC differentiation was studied in vitro , and a rat coccygeal vertebrae degeneration model was used to investigate the regenerative effect of the CCSA system on the degenerated NP in vivo . The results showed that the CCSA delivery system cross-linked with 0.02% genipin was biocompatible and promoted the expressions of NP-specific genes. After the injection of the CCSA system, the disc height, water content, extracellular matrix synthesis, and structure of the degenerated NP were partly restored. Our CCSA delivery system uses minimally invasive approaches to promote the regeneration of degenerated NP and provides an exciting new avenue for the treatment of degenerative disc disease. Statement of Significance Nucleus pulposus (NP) degeneration is usually the origin of intervertebral disc degeneration and consequent lower back pain. Stem cell-based tissue engineering is a promising method in NP regeneration, but there is a lack of viable cell carriers to transplant ADSCs into the NP while maintaining cell function. In this study, we developed a type II collagen/chondroitin sulfate (CS) composite hydrogel-like ADSC (CCSA) delivery system with genipin as the cross-linking agent. Although several research groups have studied the fabrication of injectable hydrogel with biological matrix, our study differs from other works. We chose type II collagen and CS, the two primary native components in the NP, as the main materials and combined them according to the natural ratio of collagen and sGAG in the NP. The delivery system is preloaded with ADSCs and can be injected into the NP with a needle, followed by in situ gelation . Genipin is used as a cross-linker to improve the bio-stability of the scaffold, with low cytotoxicity. We investigated the stimulatory effects of our scaffold on the differentiation of ADSCs in vitro and the regenerative effect of the CCSA delivery system on degenerated NP in vivo .
研究领域:
组织工程
·
干细胞生物学
·
再生医学
·
骨科
·
生物医学材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）