Extracellular and intracellular mechanisms of mechanotransduction in three-dimensionally embedded rat chondrocytes.

Purpose:Articular cartilage homeostasis involves modulation of chondrocyte matrix synthesis in response to mechanical stress (MS). We studied extracellular and intracellular mechanotransduction pathways mediating this response.Methods:We first confirmed rapid up-regulation of the putative chondro-protective cytokine, interleukin (IL)-4, as an immediate response to MS. We then studied the role of IL-4 by investigating responses to exogenous IL-4 or a specific IL-4 inhibitor, combined with MS. Next we investigated the intracellular second messengers. Since chondrocyte phenotype alters according to the extracellular environment, we characterized the response to mechanotransduction in 3-dimensionally embedded chondrocytes.Results:Expression of aggrecan and type II collagen was significantly up-regulated by exogenous IL-4 whereas MS-induced matrix synthesis was inhibited by an IL-4 blocker. Further, MS-induced matrix synthesis was completely blocked by a p38 MAPK inhibitor, while it was only partially blocked by inhibitors of other putative second messengers.Conclusion:IL-4 mediates an extracellular pathway of mechanotransduction, perhaps via an autocrine/paracrine loop, while p38 mediates an intracellular pathway prevalent only in a 3-dimensional environment.滋賀医科大学平成29年

Effect of dynamic compressive loading and its combination with a growth factor on the chondrocytic phenotype of 3-dimensional scaffold-embedded chondrocytes

Background and purpose Three-dimensionally (3D-) embedded chondrocytes have been suggested to maintain the chondrocytic phenotype. Furthermore, mechanical stress and growth factors have been found to be capable of enhancing cell proliferation and ECM synthesis. We investigated the effect of mechanical loading and growth factors on reactivation of the 3D-embedded chondrocytes

Effects of mechanical stress and the p38 inhibitor SB203580 on aggrecan and type II collagen mRNA expression during mechanical loading.

<p>(A) Effect of MS combined with the p38 inhibitor SB203580 on AGC gene expression at different concentrations (10, 20 µM). (B) Effect of the p38 inhibitor SB203580 on Col2 gene expression. All data are shown as relative means (95% C.I.), n = 7. * <i>P</i><0.05 versus NS, ** <i>P</i><0.05 versus MS by one-factor ANOVA.</p

Interleukin-4-induced up-regulation of aggrecan and type II collagen.

<p>Effects of IL-4 on relative expression of (A) AGC, and (B) Col2 by chondrocytes in a 3D matrix with 10 ng/mL IL-4 were assessed at 1, 7, 13, and 25 h by real-time RT-PCR. Results are expressed as mean (95% C.I.), n = 7. Means were compared by one-factor ANOVA. *<i>P</i><0.05 versus NS.</p

Inhibition of mechanical stress-induced up-regulation of aggrecan and type II collagen by adding soluble IL-4 receptor.

<p>(A) Schematic diagram showing putative mechanotransduction pathways in 3D-embedded chondrocytes following mechanical stimulation. (B) Effect of IL-4 inhibitors on 3D-embedded chondrocytes during mechanical loading. Dynamic compressive loading (60 min/day) was applied in combination with soluble IL-4 receptor (sIL-4R) at a range of concentrations (1, 10, 100, and 1000 ng/mL). (C) Effect of soluble IL-4 receptor (sIL-4R) on type II collagen (Col2) gene expression. All data are shown as mean (relative to GAPDH, 95% C.I.). n = 7. *<i>P</i><0.05 versus NS by one-factor ANOVA.</p

Mechanical stress-induced up-regulation of interleukin-4 gene expression.

<p>IL-4 gene expression by 3D-embedded, mechanically stressed (60 min/day), chondrocytes was analyzed by real time RT-PCR.</p

Mechanical stress-induced up-regulation of aggrecan and type II collagen.

<p>Effects of MS (60 min/day) on relative expression of (A) aggrecan (AGC), and (B) type II collagen (Col2) by chondrocytes in a 3D matrix were assessed at 1, 7, 13, and 25 h by real-time RT-PCR. Results are expressed as mean (95% C.I.), n = 7. Means were compared by one-factor ANOVA. *<i>P</i><0.05 versus NS.</p

Effects of MAPK inhibitors on aggrecan and type II collagen expression during mechanical loading.

<p>(A) Effect of the ERK pathway inhibitor UO126 (25 µM) on AGC expression. (B) Effect of UO126 on Col2 expression. (C) Effect of the JNK inhibitor SP600125 on AGC expression at different concentrations (10, 20 µM). (D) Effect of SP600125 on Col2 expression. All data are shown as relative means (95% C.I.), n = 7. * <i>P</i><0.05 versus NS, ** <i>P</i><0.05 versus MS by one-factor ANOVA.</p

Total knee arthroplasty for treatment of osteoarthritis with prolonged patellar dislocation

Prolonged dislocation of the patella is a rare condition and is often related to severe osteoarthritis (OA) of the femorotibial (FT) joint. For this condition's treatment, numerous surgical techniques using total knee arthroplasty (TKA) have been published. To the best of our knowledge, this case report is the first description of the use of lateral release alone to treat recurrent patellar subluxation with TKA. An interesting point in this case is that the patient had a good recovery after TKA in spite of quite a long-term (a duration of almost 55 years) dislocation of her patella and development of secondary OA. We describe a case that we treated by TKA for FT-OA with a prolonged patellar dislocation. We were able to obtain good patellar reduction without additional surgery by performing adequate lateral release of the patellar retinaculum. This clinical case indicates the usefulness of lateral patellar retinaculum release for obtaining stable patellar tracking in TKA for FT-OA with remaining lateral patellar dislocation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)