Yukio Akasaki
Kyushu University
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Publication
Featured researches published by Yukio Akasaki.
Journal of Bone and Joint Surgery-british Volume | 2008
Hideki Mizu-uchi; Shuichi Matsuda; Hiromasa Miura; Ken Okazaki; Yukio Akasaki; Yukihide Iwamoto
We compared the alignment of 39 total knee replacements implanted using the conventional alignment guide system with 37 implanted using a CT-based navigation system, performed by a single surgeon. The knees were evaluated using full-length weight-bearing anteroposterior radiographs, lateral radiographs and CT scans. The mean hip-knee-ankle angle, coronal femoral component angle and coronal tibial component angle were 181.8 degrees (174.2 degrees to 188.3 degrees), 88.5 degrees (84.0 degrees to 91.8 degrees) and 89.7 degrees (86.3 degrees to 95.1 degrees), respectively for the conventional group and 180.8 degrees (178.2 degrees to 185.1 degrees), 89.3 degrees (85.8 degrees to 92.0 degrees) and 89.9 degrees (88.0 degrees to 93.0 degrees), respectively for the navigated group. The mean sagittal femoral component angle was 85.5 degrees (80.6 degrees to 92.8 degrees) for the conventional group and 89.6 degrees (85.5 degrees to 94.0 degrees) for the navigated group. The mean rotational femoral and tibial component angles were -0.7 degrees (-8.8 degrees to 9.8 degrees) and -3.3 degrees (-16.8 degrees to 5.8 degrees) for the conventional group and -0.6 degrees (-3.5 degrees to 3.0 degrees) and 0.3 degrees (-5.3 degrees to 7.7 degrees) for the navigated group. The ideal angles of all alignments in the navigated group were obtained at significantly higher rates than in the conventional group. Our results demonstrated significant improvements in component positioning with a CT-based navigation system, especially with respect to rotational alignment.
Osteoarthritis and Cartilage | 2009
Yukio Akasaki; S. Matsuda; Keiichi I. Nakayama; Shingo Fukagawa; Hiromasa Miura; Yukihide Iwamoto
OBJECTIVE To examine the therapeutic efficacy of an HMG-CoA reductase inhibitor (statin) in rabbit osteoarthritis (OA) in vitro and in vivo. METHODS In the presence or absence of mevastatin, rabbit chondrocytes and synoviocytes were incubated with Interleukin-1beta (IL-1beta), and analyzed by biochemical methods. Thirty-two mature rabbits that underwent bilateral anterior cruciate ligament transaction (ACLT) received six consecutive weekly intra-articular injections of mevastatin at three different concentrations or a control solution. All animals were sacrificed 6 weeks after ACLT, and the knee joints were assessed by morphological, histological, immunohistochemical, and biochemical methods. RESULTS Mevastatin inhibited IL-1beta stimulation of gene expression of monocyte chemoattractant protein-1 (MCP-1) and matrix-metalloproteinases 3 (MMP-3), in synoviocytes but not chondrocytes. The levels of MCP-1 and MMP-3 productions in synoviocytes were significantly reduced by statin-treatment. In rabbit with OA, intra-articular injection of mevastatin significantly reduced cartilage degradation, as assessed by morphological and histological examinations. Synovial tissues of knees treated with mevastatin showed less severe inflammatory responses with reduced thickness of synovial cell lining and less infiltration of subsynovial CD68+monocyte lineage cells compared to untreated control knees. Relative mRNA expressions of MCP-1, IL-1beta, MMP-3, and MMP-13 were reduced in synovial tissues, but not articular cartilage, of knees treated with mevastatin compared with untreated control knees. CONCLUSION During the development of experimental OA, intra-articular administration of HMG-CoA reductase inhibitor (statin) reduces inflammatory cell infiltration and matrix-degrading enzyme expression, thus limiting cartilage degradation.
Arthritis & Rheumatism | 2013
B. Caramés; William B. Kiosses; Yukio Akasaki; Diana C. Brinson; William Eap; James A. Koziol; Martin Lotz
OBJECTIVE Aging-associated changes in articular cartilage represent a main risk factor for osteoarthritis (OA). Autophagy is an essential cellular homeostasis mechanism. Aging-associated or experimentally induced defects in autophagy contribute to organismal- and tissue-specific aging, while enhancement of autophagy may protect against certain aging-related pathologies such as OA. The objective of this study was to determine whether glucosamine can activate autophagy. METHODS Chondrocytes from normal human articular cartilage were treated with glucosamine (0.1- 10 mM). Autophagy activation and phosphorylation levels of Akt, FoxO3, and ribosomal protein S6 were determined by Western blotting. Autophagosome formation was analyzed by confocal microscopy. Reporter mice systemically expressing green fluorescent protein (GFP) fused to light chain 3 (LC3) (GFP-LC3-transgenic mice) were used to assess changes in autophagy in response to starvation and glucosamine treatment. RESULTS Glucosamine treatment of chondrocytes activated autophagy, as indicated by increased LC3-II levels, formation of LC3 puncta, and increased LC3 turnover. This was associated with glucosamine-mediated inhibition of the Akt/FoxO3/mammalian target of rapamycin pathway. Administration of glucosamine to GFP-LC3-transgenic mice markedly activated autophagy in articular cartilage. CONCLUSION Glucosamine modulates molecular targets of the autophagy pathway in vitro and in vivo, and the enhancement of autophagy is mainly dependent on the Akt/FoxO/mTOR pathway. These findings suggest that glucosamine is an effective autophagy activator and should motivate future studies on the efficacy of glucosamine in modifying aging-related cellular changes and supporting joint health.
Arthritis & Rheumatism | 2014
Yukio Akasaki; O. Alvarez-Garcia; Masahiko Saito; B. Caramés; Yukihide Iwamoto; Martin Lotz
A major signaling pathway that regulates cellular aging is the insulin/insulin‐like growth factor 1 (IGF‐1)/phosphatidylinositol 3‐kinase (PI3K)/Akt/FoxO transcription factor axis. We previously observed that FoxO transcription factors are dysregulated in aged and OA cartilage. The objective of this study was to investigate the impact of down‐regulated FoxO transcription factors on chondrocytes.
Osteoarthritis and Cartilage | 2013
Yukio Akasaki; Akihiko Hasegawa; Masahiko Saito; Hiroshi Asahara; Yukihide Iwamoto; Martin Lotz
OBJECTIVE Aging is a major risk factor for osteoarthritis (OA). Forkhead-box class O (FoxO) transcription factors regulate mechanisms of cellular aging, including protein quality control, autophagy and defenses against oxidative stress. The objective of this study was to analyze FoxO transcription factors in normal, aging and OA cartilage. DESIGN Knee joints from humans ages 23-90 and from mice at the age of 4-24 months and following surgically induced OA were analyzed for expression of FoxO proteins. Regulation of FoxO protein expression and activation was analyzed in cultured chondrocytes. RESULTS Human cartilage expressed FOXO1 and FOXO3 but not FOXO4 proteins. FOXO1 and FOXO3 were more strongly expressed the superficial and mid zone as compared to the deep zone and were mainly localized in nuclei. During human joint aging, expression of FOXO1 and FOXO3 was markedly reduced in the superficial zone of cartilage regions exposed to maximal weight bearing. In OA cartilage, chondrocyte clusters showed strong FOXO phosphorylation and cytoplasmic localization. Similar patterns of FOXO expression in normal joints and changes in aging and OA were observed in mouse models. In cultured chondrocytes, IL-1β and TNF-α suppressed FOXO1, while TGF-β and PDGF increased FOXO1 and FOXO3 expression. FOXO1 and FOXO3 phosphorylation was increased by IL-1β, PDGF, bFGF, IGF-1, and the oxidant t-BHP. CONCLUSIONS Normal articular cartilage has a tissue specific signature of FoxO expression and activation and this is profoundly altered in aging and OA in humans and mice. Changes in FoxO expression and activation may be involved in cartilage aging and OA.
Journal of Arthroplasty | 2008
Yukio Akasaki; Shuichi Matsuda; Takeshi Shimoto; Hiromasa Miura; Hidehiko Higaki; Yukihide Iwamoto
The present study evaluated the effects of extent of conformity of post-cam design on contact area and stress at post-cam mechanism using 4 different posterior-stabilized prostheses. TRAC and Alpina with full-conformed post-cams exhibited the largest contact area at 90 degrees and 120 degrees . PFC sigma RPF with partial conformed post-cam had the largest contact area at 150 degrees . Scorpio NRG with less conformed post-cam had smaller contact area than the others. Lifting of femoral component decreased contact area and increased contact stress of TRAC and Alpina. Recent modifications of post-cam design have increased contact area, contributing to lower contact stress. None of these prostheses exhibited constant low contact stress throughout flexion. Further modifications of post-cam mechanism are necessary to provide lower contact stress throughout deep knee flexion.
Knee Surgery, Sports Traumatology, Arthroscopy | 2009
Yukio Akasaki; Shuichi Matsuda; Hiromasa Miura; Ken Okazaki; Taka Aki Moro-oka; Hideki Mizu-uchi; Yukihide Iwamoto
This study evaluated the mid-term results of total knee arthroplasty (TKA) following high tibial osteotomy (HTO), comparing posterior cruciate-retaining prostheses to posterior stabilized prostheses. The Knee Society score for the entire group (20 knees) improved significantly from 62 (median) preoperatively to 87 at the latest follow-up. The postoperative Knee Society score of 85 in posterior cruciate-retaining prostheses (8 knees) was significantly inferior to the 94 score in posterior stabilized prostheses (12 knees). Of Knee Society score, Stability and ROM scores (17 and 21, respectively) in posterior cruciate-retaining TKA were inferior to those in posterior stabilized TKA (25 and 24, respectively). Since postoperative knee instability due to posterior cruciate ligament (PCL) insufficiency is thought to contribute to the inferior results of posterior cruciate-retaining prostheses after HTO, PCL-substituting TKA would be suitable for use after HTO.
Osteoarthritis and Cartilage | 2016
O. Alvarez-Garcia; Merissa Olmer; R. Akagi; Yukio Akasaki; Kathleen M. Fisch; T. Shen; Andrew I. Su; Martin Lotz
OBJECTIVE Aging is a main risk factor for the development of osteoarthritis (OA) and the molecular mechanisms underlying the aging-related changes in articular cartilage include increased mammalian target of rapamycin (mTOR) signaling and defective autophagy. REDD1 is an endogenous inhibitor of mTOR that regulates cellular stress responses. In this study we measured REDD1 expression in normal, aged and OA cartilage and assessed REDD1 function in human and mouse articular chondrocytes. METHODS REDD1 expression was analyzed in human and mouse articular cartilage by qPCR, western blotting, and immunohistochemistry. For functional studies, REDD1 and TXNIP knockdown or overexpression was performed in chondrocytes in the presence or absence of rapamycin and chloroquine, and mTOR signaling and autophagy were measured by western blotting. REDD1/TXNIP protein interaction was assessed by co-immunoprecipitation experiments. RESULTS Human and mouse cartilage from normal knee joints expressed high levels of REDD1. REDD1 expression was significantly reduced in aged and OA cartilage. In cultured chondrocytes, REDD1 knockdown increased whereas REDD1 overexpression decreased mTOR signaling. In addition, REDD1 activated autophagy by an mTOR independent mechanism that involved protein/protein interaction with TXNIP. The REDD1/TXNIP complex was required for autophagy activation in chondrocytes. CONCLUSION The present study shows that REDD1 is highly expressed in normal human articular cartilage and reduced during aging and OA. REDD1 in human chondrocytes negatively regulates mTOR activity and is essential for autophagy activation. Reduced REDD1 expression thus represents a novel mechanism for the increased mTOR activation and defective autophagy observed in OA.
Arthritis & Rheumatism | 2015
Yukio Akasaki; Natàlia Reixach; Tokio Matsuzaki; O. Alvarez-Garcia; Merissa Olmer; Yukihide Iwamoto; Joel N. Buxbaum; Martin Lotz
Amyloid deposits are prevalent in osteoarthritic (OA) joints. We undertook this study to define the dominant precursor and to determine whether the deposits affect chondrocyte functions.
Science Translational Medicine | 2018
Tokio Matsuzaki; O. Alvarez-Garcia; Sho Mokuda; Keita Nagira; Merissa Olmer; Ramya Gamini; Kohei Miyata; Yukio Akasaki; Andrew I. Su; Hiroshi Asahara; Martin Lotz
FoxO play a key role in postnatal cartilage development, maturation, homeostasis, and osteoarthritis pathogenesis. Clever as a FoxO FoxO proteins are transcription factors that regulate autophagy, metabolism, and aging. Matsuzaki et al. investigated the role of different FoxO in cartilage development, homeostasis, and degeneration during osteoarthritis. Cartilage was thicker and chondrocytes were more proliferative in young mice lacking FoxO1/3/4 in cartilage. Chondrocyte-specific FoxO-deficient mice exhibited worse arthritis with aging and increased cartilage degradation in response to surgically induced arthritis; they also expressed less lubricin, a protein that helps reduce friction in joints. FoxO1 and autophagy-related genes were reduced in human chondrocytes from patients with osteoarthritis, and restoring FoxO1 expression reduced inflammatory cytokines and up-regulated lubricin. This study suggests that FoxO factors could be targets for therapy in osteoarthritis. Aging is a main risk factor for osteoarthritis (OA). FoxO transcription factors protect against cellular and organismal aging, and FoxO expression in cartilage is reduced with aging and in OA. To investigate the role of FoxO in cartilage, Col2Cre-FoxO1, 3, and 4 single knockout (KO) and triple KO mice (Col2Cre-TKO) were analyzed. Articular cartilage in Col2Cre-TKO and Col2Cre-FoxO1 KO mice was thicker than in control mice at 1 or 2 months of age. This was associated with increased proliferation of chondrocytes of Col2Cre-TKO mice in vivo and in vitro. OA-like changes developed in cartilage, synovium, and subchondral bone between 4 and 6 months of age in Col2Cre-TKO and Col2Cre-FoxO1 KO mice. Col2Cre-FoxO3 and FoxO4 KO mice showed no cartilage abnormalities until 18 months of age when Col2Cre-FoxO3 KO mice had more severe OA than control mice. Autophagy and antioxidant defense genes were reduced in Col2Cre-TKO mice. Deletion of FoxO1/3/4 in mature mice using Aggrecan(Acan)-CreERT2 (AcanCreERT-TKO) also led to spontaneous cartilage degradation and increased OA severity in a surgical model or treadmill running. The superficial zone of knee articular cartilage of Col2Cre-TKO and AcanCreERT-TKO mice exhibited reduced cell density and markedly decreased Prg4. In vitro, ectopic FoxO1 expression increased Prg4 and synergized with transforming growth factor–β stimulation. In OA chondrocytes, overexpression of FoxO1 reduced inflammatory mediators and cartilage-degrading enzymes, increased protective genes, and antagonized interleukin-1β effects. Our observations suggest that FoxO play a key role in postnatal cartilage development, maturation, and homeostasis and protect against OA-associated cartilage damage.