Abstract:Hyaluronan (HA) and superficial zone protein (SZP) distribute in joint structures and play a crucial role in joint lubrication. The aim of this study was to examine the effect of fluid flow on the synthesis of both HA and SZP in synovial membrane cells. Shear stress was applied by fluid flow to the rabbit synovial membrane cell line, HIG-82. The mRNA levels of HA synthase 2 (HAS2) , HA synthase 3 (HAS3), and SZP were examined by real-time PCR. The levels of HA and SZP protein were determined by sandwich ELISA … Show more
“…As HYAL1 and HYAL2 mRNA levels were upregulated in the presence of IL‐1β, resulting in enhanced HYAL activity 18 . High‐magnitude shear stress decreased expression of both HAS2 and HAS3, accompanied by reduced HA synthesis 19 . A single intra‐articular injection of diclofenac etalhyaluronate (SI‐613) was capable of inducing the production of high molecular weight HA in synoviocytes from OA patients.…”
Hyaluronic acid (HA) exerts a critical role in the lubricating and buffering properties of synovial fluid in joints. The production of HA is regulated by growth factors, hormones, inflammatory cytokines and mechanical load. The reduction of HA contributes to the progression of osteoarthritis. Herein, we found that d‐galactose (d‐gal) induced the senescence of rabbit synovial membrane cells, accompanied by decreased HA production. The mRNA level of HA synthase 2 (HAS2) was downregulated by d‐gal, as analysed by real‐time polymerase chain reaction. Melatonin, an endocrine hormone, can regulate the homeostasis of bone and cartilage. We found that melatonin treatment attenuated d‐gal‐induced cell senescence and decreased the expression of p21, p16 and pp65 proteins. Melatonin could reverse HA production and maintain HAS2 expression. Furthermore, we revealed that Sirt1 signalling was required for melatonin effects. Sirt1 inhibitor could counteract melatonin‐mediated HA production and HAS2 expression. Additionally, Sirt1 overexpression directly antagonized d‐gal‐induced cell aging and HA downregulation. Taken together, our results suggest that melatonin‐Sirt1 signal has a protective effect on synovial membrane cells, enhancing HA synthesis and interrupting cell senescence.
“…As HYAL1 and HYAL2 mRNA levels were upregulated in the presence of IL‐1β, resulting in enhanced HYAL activity 18 . High‐magnitude shear stress decreased expression of both HAS2 and HAS3, accompanied by reduced HA synthesis 19 . A single intra‐articular injection of diclofenac etalhyaluronate (SI‐613) was capable of inducing the production of high molecular weight HA in synoviocytes from OA patients.…”
Hyaluronic acid (HA) exerts a critical role in the lubricating and buffering properties of synovial fluid in joints. The production of HA is regulated by growth factors, hormones, inflammatory cytokines and mechanical load. The reduction of HA contributes to the progression of osteoarthritis. Herein, we found that d‐galactose (d‐gal) induced the senescence of rabbit synovial membrane cells, accompanied by decreased HA production. The mRNA level of HA synthase 2 (HAS2) was downregulated by d‐gal, as analysed by real‐time polymerase chain reaction. Melatonin, an endocrine hormone, can regulate the homeostasis of bone and cartilage. We found that melatonin treatment attenuated d‐gal‐induced cell senescence and decreased the expression of p21, p16 and pp65 proteins. Melatonin could reverse HA production and maintain HAS2 expression. Furthermore, we revealed that Sirt1 signalling was required for melatonin effects. Sirt1 inhibitor could counteract melatonin‐mediated HA production and HAS2 expression. Additionally, Sirt1 overexpression directly antagonized d‐gal‐induced cell aging and HA downregulation. Taken together, our results suggest that melatonin‐Sirt1 signal has a protective effect on synovial membrane cells, enhancing HA synthesis and interrupting cell senescence.
“…Phagocytosis, cell surface binding and actin reorganization together may affect how FLS synthesize other molecules beyond the ECM proteins or inflammatory factors studied here in response to physical stimuli presented to FLS in the synovial joint environment (e.g. fluid shear or mechanical stretch) 48–50 .…”
Objective
Arthroscopy with lavage and synovectomy can remove tissue debris from the joint space and the synovial lining to provide pain relief to patients with osteoarthritis (OA). Here, we developed an in vitro model to study the interaction of cartilage wear particles with fibroblast-like synoviocytes (FLS) to better understand the interplay of cartilage particulates with cytokines on cells of the synovium.
Method
In this study sub-10μm cartilage particles or 1μm latex particles were co-cultured with FLS ± 10 ng/mL interleukin-1α (IL-1 α) or tumor necrosis factor- α (TNF-α). Samples were analyzed for DNA, glycosaminoglycan (GAG), and collagen and media samples were analyzed for media GAG, nitric oxide (NO) and prostaglandin-E2 (PGE2). The nature of the physical interaction between the particles and FLS was determined by microscopy.
Results
Both latex and cartilage particles could be phagocytosed by FLS. Cartilage particles were internalized and attached to the surface of both dense monolayers and individual cells. Co-culture of FLS with cartilage particulates resulted in a significant increase in cell sheet DNA and collagen content as well as NO and PGE2 synthesis compared to control and latex treated groups.
Conclusion
The proliferative response of FLS to cartilage wear particles resulted in an overall increase in ECM content, analogous to the thickening of the synovial lining observed in OA patients. Understanding how cartilage particles interface with the synovium may provide insight into how this interaction contributes to OA progression and may guide the role of lavage and synovectomy for degenerative disease.
“…HA is reported to protect against apoptosis and to promote survival in various types of cells, including granulosa cells (44), articular chondrocytes (45,46), and human aortic smooth muscle cells (37). In contrast, other studies showed that HA treatment induces cell death in cultured human gingival fibroblasts (47) and lymphoma cell lines (48). Thus, the regulatory effect of HA upon cell viability appears to depend upon cell context, even when controlling for the size of HA, because high molecular weight HA has been shown to either promote cellular survival (37) or induce cell death (49) in different cell types.…”
Background: Hyaluronan (HA), an extracellular glycosaminoglycan, is normally produced by three HA synthase (Has) enzymes. Results: Skin fibroblasts from Has1/Has3 double knock-out mice have higher Has2 expression and HA levels and are resistant to cell death after UVB exposure or serum starvation. Conclusion: HA modulates injury-induced apoptotic responses in fibroblasts. Significance: HA has an important role in cell death responses.
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