Oscillatory fluid flow regulates glycosaminoglycan production via an intracellular calcium pathway in meniscal cells

Eifler, Robert L.; Blough, Eric R.; Dehlin, Jennifer M.; Donahue, Tammy L. Haut

doi:10.1002/jor.20028

Cited by 22 publications

(15 citation statements)

References 48 publications

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“…Interestingly, while shear is generally thought of as detrimental to the chondrocyte phenotype, oscillatory fluid flow has been shown to upregulate calcium signaling and GAG production of meniscus cells in parallel plate flow chambers [279]. The use of shear and other forces to generate fibrocartilage may yield benefits for meniscus tissue engineering in the future.…”

Section: Mechanical Stimulation For Meniscus Tissue Engineeringmentioning

confidence: 99%

The knee meniscus: Structure–function, pathophysiology, current repair techniques, and prospects for regeneration

2011

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Extensive scientific investigations in recent decades have established the anatomical, biomechanical, and functional importance that the meniscus holds within the knee joint. As a vital part of the joint, it acts to prevent the deterioration and degeneration of articular cartilage, and the onset and development of osteoarthritis. For this reason, research into meniscus repair has been the recipient of particular interest from the orthopedic and bioengineering communities. Current repair techniques are only effective in treating lesions located in the peripheral vascularized region of the meniscus. Healing lesions found in the inner avascular region, which functions under a highly demanding mechanical environment, is considered to be a significant challenge. An adequate treatment approach has yet to be established, though many attempts have been undertaken. The current primary method for treatment is partial meniscectomy, which commonly results in the progressive development of osteoarthritis. This drawback has shifted research interest towards the fields of biomaterials and bioengineering, where it is hoped that meniscal deterioration can be tackled with the help of tissue engineering. So far, different approaches and strategies have contributed to the in vitro generation of meniscus constructs, which are capable of restoring meniscal lesions to some extent, both functionally as well as anatomically. The selection of the appropriate cell source (autologous, allogeneic, or xenogeneic cells, or stem cells) is undoubtedly regarded as key to successful meniscal tissue engineering. Furthermore, a large variation of scaffolds for tissue engineering have been proposed and produced in experimental and clinical studies, although a few problems with these (e.g., byproducts of degradation, stress shielding) have shifted research interest towards new strategies (e.g., scaffoldless approaches, self-assembly). A large number of different chemical (e.g., TGF-β1, C-ABC) and mechanical stimuli (e.g., direct compression, hydrostatic pressure) have also been investigated, both in terms of encouraging functional tissue formation, as well as in differentiating stem cells. Even though the problems accompanying meniscus tissue engineering research are considerable, we are undoubtedly in the dawn of a new era, whereby recent advances in biology, engineering, and medicine are leading to the successful treatment of meniscal lesions.

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Section: Mechanical Stimulation For Meniscus Tissue Engineeringmentioning

confidence: 99%

The knee meniscus: Structure–function, pathophysiology, current repair techniques, and prospects for regeneration

2011

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“…Calcium is an ubiquitous second messenger that is one of the earliest cell signaling events triggered by applied physical and chemical stimuli (Yellowley, Jacobs et al 1999). Intracellular calcium transients in response to fluid-induced shear have been observed for cells residing in a variety of musculoskeletal tissues, including bone (Hung, Pollack et al 1995, Jacobs, Yellowley et al 1998), ligament (Hung, Allen et al 1997), tendon (Wall and Banes 2005), meniscus (Eifler, Blough et al 2006) and cartilage (Edlich, Yellowley et al 2001). Toward efforts to better understand the underlying mechanisms that mediate the shear-induced calcium response, a subset of studies was undertaken to determine the role of extracellular and intracellular calcium sources.…”

Section: Introductionmentioning

confidence: 99%

Fibroblast-like synoviocyte mechanosensitivity to fluid shear is modulated by interleukin-1α

Estell

Murphy

Silverstein

et al. 2017

Journal of Biomechanics

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Fibroblast-like synoviocytes (FLS) reside in the synovial membrane of diarthrodial joints and are exposed to a dynamic fluid environment that presents both physical and chemical stimuli. The ability of FLS to sense and respond to these stimuli plays a key role in their normal function, and is implicated in the alterations to function that occur in osteoarthritis (OA). The present work characterizes the response of FLS to fluid flow-induced shear stress via real-time calcium imaging, and tests the hypothesis that this response is modulated by interleukin-1α (IL-1α), a cytokine elevated in OA. FLS demonstrated a robust calcium signaling response to fluid shear that was dose dependent upon stress level and required both external and internal calcium sources. Preconditioning with 10 ng/mL IL-1α for 24 hrs heightened this shear stress response by significantly increasing the percent of responding cells and peak magnitude, while significantly decreasing the time for a peak to occur. Intercellular communication via gap junctions was found to account for a portion of the FLS population response in normal conditions, and was significantly increased by IL-1α preconditioning. IL-1α was also found to significantly increase average length and incidence of the primary cilia, an organelle commonly implicated in shear mechanosensing. These findings suggest that the elevated levels of IL-1α found in the OA environment heighten FLS sensitivity to fluid shear by altering both intercellular communication and individual cell sensitivity, which could affect downstream functions and contribute to progression of the disease state.

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“…Studies of matrix synthesis during dynamic compression of intact cartilage and chondrocytes in 3D scaffolds strongly suggest that fluid flow plays an important role in regulating chondrocyte metabolism 5. Fluid flow in has been shown to modulate chondrocyte Ca 2+ signaling pathways and synthesis of matrix proteins in monolayer6 as well as in 3D‐scaffold cultured chondrocytes in perfusion bioreactors 7, 8. The effects of fluid flow on chondrocytes may be regulated by an intracellular calcium signaling pathway suggested to regulate glycosaminoglycan metabolism 6.…”

mentioning

confidence: 99%

“…Fluid flow in has been shown to modulate chondrocyte Ca 2+ signaling pathways and synthesis of matrix proteins in monolayer6 as well as in 3D‐scaffold cultured chondrocytes in perfusion bioreactors 7, 8. The effects of fluid flow on chondrocytes may be regulated by an intracellular calcium signaling pathway suggested to regulate glycosaminoglycan metabolism 6. Chondrocyte Ca 2+ signaling increases in a dose dependent manner in response to fluid flow in monolayer cultures 9, 10.…”

mentioning

confidence: 99%

Calcium signaling in response to fluid flow by chondrocytes in 3D alginate culture

Degala

Williams

Zipfel

et al. 2011

Journal Orthopaedic Research

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Quantifying the effects of mechanical loading on the metabolic response of chondrocytes is difficult due to complicated structure of cartilage ECM and the coupled nature of the mechanical stimuli presented to the cells. In this study we describe the effects of fluid flow, particularly hydrostatic pressure and wall shear stress, on the Ca 2þ signaling response of bovine articular chondrocytes in 3D culture. Using well-established alginate hydrogel system to maintain spherical chondrocyte morphology, we altered solid volume fraction to change scaffold mechanics. Fluid velocities in the bulk of the scaffolds were directly measured via an optical technique and scaffold permeability and aggregate modulus was characterized to quantify the mechanical stimuli presented to cells. Ca 2þ signaling response to direct perfusion of chondrocyte-seeded scaffolds increased monotonically with flow rate and was found more directly dependent on fluid velocity rather than shear stress or hydrostatic pressure. Chondrocytes in alginate scaffolds responded to fluid flow at velocities and shear stresses 2-3 orders of magnitude lower than seen in previous monolayer studies. Our data suggest that flow-induced Ca 2þ signaling response of chondrocytes in alginate culture may be due to mechanical signaling pathways, which is influenced by the 3D nature of cell shape. ß

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Oscillatory fluid flow regulates glycosaminoglycan production via an intracellular calcium pathway in meniscal cells

Cited by 22 publications

References 48 publications

The knee meniscus: Structure–function, pathophysiology, current repair techniques, and prospects for regeneration

The knee meniscus: Structure–function, pathophysiology, current repair techniques, and prospects for regeneration

Fibroblast-like synoviocyte mechanosensitivity to fluid shear is modulated by interleukin-1α

Calcium signaling in response to fluid flow by chondrocytes in 3D alginate culture

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