Dataset Information

Lubricin-Inspired Janus Hydrogel Microspheres with Enhanced Lubrication and Anti-Inflammation through Cartilage Adhesion for Osteoarthritis Treatment

ABSTRACT: Osteoarthritis (OA), a prevalent, disabling degenerative joint disorder, progresses due to cartilage lubrication failure and excessive inflammation. Inspired by the structure and function of natural lubricin on cartilage surface, this study develops Janus hydrogel microspheres with independent, asymmetric adhesive and lubricating compartments (Janus-Cur@Ms) via a biofriendly oil-free microfluidic platform. The spatially decoupled adhesive and lubricating functionalities enable stable cartilage adhesion, reduced off-target effect, and enhanced lubrication performance, thus overcoming the inherent conflict between adhesion and lubrication. This adhesion-enhanced lubrication synergizes with the anti-inflammatory effect of loaded curcumin, producing a combined therapeutic effect against OA. In vitro, Janus-Cur@Ms promote anabolism and suppress catabolism in primary chondrocytes, thereby restoring cellular function. In a rabbit OA model, Janus-Cur@Ms alleviate cartilage injury, delay joint space narrowing, inhibits pathological subchondral bone resorption, and reduces cartilage matrix loss, collectively attenuating OA progression. In summary, Janus-Cur@Ms simultaneously address multiple pathological hallmarks of OA through synergistic adhesion-enhanced lubrication and anti-inflammatory effects, demonstrating significant therapeutic efficacy.

ORGANISM(S): Oryctolagus Cuniculus

SUBMITTER: Zongke Zhou

PROVIDER: PXD073749 | iProX | Thu Jan 29 00:00:00 GMT 2026

REPOSITORIES: iProX

ACCESS DATA

Similar Datasets

Project description:Baker2017 - The role of cytokines, MMPs and fibronectin fragments osteoarthritis This model is described in the article: Mathematical modelling of cytokines, MMPs and fibronectin fragments in osteoarthritic cartilage. Baker M, Brook BS, Owen MR. J Math Biol 2017 Feb; : Abstract: Osteoarthritis (OA) is a degenerative disease which causes pain and stiffness in joints. OA progresses through excessive degradation of joint cartilage, eventually leading to significant joint degeneration and loss of function. Cytokines, a group of cell signalling proteins, present in raised concentrations in OA joints, can be classified into pro-inflammatory and anti-inflammatory groups. They mediate cartilage degradation through several mechanisms, primarily the up-regulation of matrix metalloproteinases (MMPs), a group of collagen-degrading enzymes. In this paper we show that the interactions of cytokines within cartilage have a crucial role to play in OA progression and treatment. We develop a four-variable ordinary differential equation model for the interactions between pro- and anti-inflammatory cytokines, MMPs and fibronectin fragments (Fn-fs), a by-product of cartilage degradation and up-regulator of cytokines. We show that the model has four classes of dynamic behaviour: homoeostasis, bistable inflammation, tristable inflammation and persistent inflammation. We show that positive and negative feedbacks controlling cytokine production rates can determine either a pre-disposition to OA or initiation of OA. Further, we show that manipulation of cytokine, MMP and Fn-fs levels can be used to treat OA, but we suggest that multiple treatment targets may be essential to halt or slow disease progression. This model is hosted on BioModels Database and identified by: MODEL1704120000. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Project description:As the most common degenerative joint disease, osteoarthritis (OA) contributes significantly to pain and disability during aging. Several genes of interest involved in articular cartilage damage in OA have been identified. However, the direct causes of OA are poorly understood. Evaluating the public human RNA-seq dataset showed that Cbfβ, (subunit of a heterodimeric Cbfβ/Runx1,Runx2, or Runx3 complex) expression is decreased in the cartilage of patients with OA. Here, we found that the chondrocyte-specific deletion of Cbfβ in tamoxifen-induced Cbfβf/fCol2α1-CreERT mice caused a spontaneous OA phenotype, worn articular cartilage, increased inflammation, and osteophytes. RNA-sequencing analysis showed that Cbfβ deficiency in articular cartilage resulted in reduced cartilage regeneration, increased canonical Wnt signaling and inflammatory response, and decreased Hippo/YAP signaling and TGF-β signaling. Immunostaining and western blot validated these RNA-seq analysis results. ACLT surgery-induced OA decreased Cbfβ and Yap expression and increased active β-catenin expression in articular cartilage, while local AAV-mediated Cbfβ overexpression promoted Yap expression and diminished active β-catenin expression in OA lesions. Remarkably, AAV-mediated Cbfβ overexpression in knee joints of mice with OA showed the significant protective effect of Cbfβ on articular cartilage in the ACLT OA mouse model. Overall, this study, using loss-of-function and gain-of-function approaches, uncovered that low expression of Cbfβ may be the cause of OA. Moreover, Local admission of Cbfβ may rescue and protect OA through decreasing Wnt/β-catenin signaling, and increasing Hippo/Yap signaling and TGFβ/Smad2/3 signaling in OA articular cartilage, indicating that local Cbfβ overexpression could be an effective strategy for treatment of OA. Using unbiased genome-wide RNA-seq data from Cbfβf/f;Col2α1-Cre hip joint articular cartilage and Cbfβf/f;Aggrecan-cre knee joint articular cartilage and their controls, we examined Cbfβ-mediated transcriptional targets for articular cartilage regeneration in OA.

Project description:Menisci play a vital role in load transmission, shock absorption and joint stability. The current dogma is that the menisci simply protects the cartilage and play no role in osteoarthritis (OA) unless they are injured. However, there is increasing evidence suggesting that OA menisci may not merely be bystanders in the disease process of OA. This study sought: 1) to determine the prevalence of meniscal degeneration in OA patients, 2) to examine gene expression in OA meniscal cells compared to normal control meniscal cells, and 3) to test the hypothesis that OA meniscal cells are different from normal meniscal cells. The grades of meniscal degeneration correlated in a positive fashion with the grades of articular cartilage degeneration (r = 0.672; P < 0.0001). Many genes classified in the biological processes of immune response, inflammatory response, biomineral formation and cell proliferation, including major histocompatibility complex, class II, DP alpha 1 (HLA-DPA1), integrin, beta 2 (ITGB2), ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), ankylosis, progressive homolog (ANKH) and fibroblast growth factor 7 (FGF7), were expressed at higher levels compared to normal control meniscal cells. In addition, many genes that were previously implicated in OA were also expressed at higher levels in OA meniscal cells, including ADAM metallopeptidase with thrombospondin type 1 motif, 5 (ADAMTS5). Our findings suggest that OA is a whole joint disease. Meniscal cells may play an active role in the development of OA. Investigation of the gene expression profiles of OA meniscal cells may reveal new therapeutic targets for OA therapy and also may uncover novel disease markers for early diagnosis of OA. Studies were approved by our human subjects Institutional Review Board. Menisci and articular cartilage were collected during joint replacement surgery for OA patients (OA specimens) and lower limb amputation surgery for osteosarcoma patients (normal control specimens), and graded. Meniscal cells were prepared from the meniscal tissues and expanded in monolayer culture. Differential gene expression in OA meniscal cells and normal control meniscal cells was examined using Affymetrix microarray and real time RT-PCR.

Dataset Information

Lubricin-Inspired Janus Hydrogel Microspheres with Enhanced Lubrication and Anti-Inflammation through Cartilage Adhesion for Osteoarthritis Treatment

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets