Tomoki Aoyama

Genetically matched human iPS cells reveal that propensity for cartilage and bone differentiation differs with clones, not cell type of origin.

Background For regenerative therapy using induced pluripotent stem cell (iPSC) technology, cell type of origin to be reprogrammed should be chosen based on accessibility and reprogramming efficiency. Some studies report that iPSCs exhibited a preference for differentiation into their original cell lineages, while others did not. Therefore, the type of cell which is most appropriate as a source for iPSCs needs to be clarified. Methodology/Principal Findings Genetically matched human iPSCs from different origins were generated using bone marrow stromal cells (BMSCs) and dermal fibroblasts (DFs) of the same donor, and global gene expression profile, DNA methylation status, and differentiation properties into the chondrogenic and osteogenic lineage of each clone were analyzed. Although genome-wide profiling of DNA methylation suggested tissue memory in iPSCs, genes expressed differentially in BMSCs and DFs were equally silenced in our bona fide iPSCs. After cell-autonomous and induced differentiation, each iPSC clone exhibited various differentiation properties, which did not correlate with cell-of-origin. Conclusions/Significance The reprogramming process may remove the difference between DFs and BMSCs at least for chondrogenic and osteogenic differentiation. Qualified and genetically matched human iPSC clone sets established in this study are valuable resources for further basic study of clonal differences.

Relationship between depression and risk of malnutrition among community-dwelling young-old and old-old elderly people

Objectives: This study explores the association between nutritional status and depression among healthy community-dwelling young-old (aged 65–74) and old-old elderly (aged 75 and older). Method: A cross-sectional design was implemented. A total of 274 community-dwelling older individuals (142 young-old; 132 old-old) were assessed using the Geriatric Depression Scale (GDS), Mini-Nutritional Assessment Short-Form (MNA-SF) and Life-Space Assessment. Logistic regression analysis was used to determine if depression was independently associated with risk of malnutrition, stratified by age (young-old vs. old-old). Results: In the logistic regression model for young-old, being at risk of malnutrition (MNA-SF (≦11) was strongly associated with depression (GDS (≧5;) (likelihood ratio νu2009=u20096.26; 95% confidence interval [CI]: 1.91–20.49). In contrast, in the old-old group, the model was not statistically significant. Conclusion: Depression and nutritional status were strongly correlated in young-old but not in old-old community-dwelling elderly. This study reveals that not only the factors correlated with but also the symptoms of depression may vary among different age stratifications of the elderly.

Destabilization of the medial meniscus leads to subchondral bone defects and site-specific cartilage degeneration in an experimental rat model.

OBJECTIVEnThis study aimed to investigate subchondral bone changes using micro-computed tomography (micro-CT) and regional differences in articular cartilage degeneration, focusing on changes of cartilage covered by menisci, in the early phase using a destabilization of the medial meniscus (DMM) model.nnnMETHODnThe DMM model was created as an experimental rat osteoarthritis (OA) model (12 weeks old; n = 24). At 1, 2, and 4 weeks after surgery, the rats were sacrificed, and knee joints were scanned using a Micro-CT system. Histological sections of the medial tibial plateau, which was divided into inner, middle, and outer regions, were prepared and scored using the modified OARSI scoring system. The cartilage thickness was also calculated, and matrix metalloproteinase 13 (MMP13), Col2-3/4c, and vascular endothelial growth factor (VEGF) expression was assessed immunohistochemically.nnnRESULTSnSubchondral bone defects were observed in the middle region, in which the cartilage thickness decreased over time after surgery, and these defects were filled with MMP13- and VEGF-expressing fibrous tissue. The OARSI score increased over time in the middle region, and the score was significantly higher in the middle region than in the inner and outer regions at 1, 2, and 4 weeks after surgery. Col2-3/4c and MMP13 expression was observed primarily in the meniscus-covered outer region, in which the cartilage thickness increased over time.nnnCONCLUSIONnLoss of meniscal function caused cartilage degeneration and subchondral bone defects in the early phase site-specifically in the middle region. Furthermore, our results might indicate cartilage covered by menisci is easily degraded resulting in osmotic swelling of the cartilage in early OA.

Rhythmic stepping exercise under cognitive conditions improves fall risk factors in community-dwelling older adults: Preliminary results of a cluster-randomized controlled trial

Objective: The purpose of this pilot trial was to evaluate whether a 24-week program of rhythmic stepping exercise (RSE) would be effective in improving physical function and reducing fear of falling in older adults. Participants: Four units (nu2009=u200952) randomized into an RSE group (two units, nu2009=u200925) and a non-rhythmic stepping exercise (NRSE) group (two units, nu2009=u200927) participated in a pilot cluster randomized controlled trial. Methods: Each exercise group received 60u2009min group training sessions once a week for 24 weeks. Measurement was based on the difference in physical functions between the RSE and NRSE groups. Results: Significant differences were observed between the two groups for locomotive function with significant groupu2009×u2009time interaction. Relative risk was calculated as 2.778 (95% CI: 1.030–7.492) for fear of falling for participants in the NRSE group compared with patients in the RSE group (pu2009=u20090.037). Conclusions: The results of this pilot trial suggest that the RSE program is more effective in improving locomotive function and fear of falling.

The layered structure of the articular surface

OBJECTIVEnArticular cartilage is roughly separated into three areas: the tangential, middle, and deep zones. The structure and molecular components of an additional important zone, the most superficial zone (MSZ), which directly faces the joint cavity, have yet to be conclusively elucidated. The purpose of the present study was to use multiple methods to study the MSZ in order to determine its structure.nnnMATERIALS AND METHODSnKnees from 16 pigs (age, 6 months) were used. Full-thickness cartilage specimens were harvested from the femoral groove. The MSZ was observed using light microscopy, transmission electron microscopy (TEM), and scanning electron microscopy (SEM) in combination with histochemical and immunohistochemical methods.nnnRESULTSnThe combined findings from the three different observational methods indicate that the MSZ is subdivided into three layers. Among these three layers, collagen subtypes I, II, and III are present in the innermost (third) layer of the MSZ. Beneath the third layer, type II collagen is the predominant type, with small amounts of type III collagen. This layer beneath the third layer is considered to be the tangential layer.nnnCONCLUSIONSnOur observations indicate that the MSZ is subdivided into three layers. Further analysis of the molecular components in each layer may improve our understanding of the structure of the articular surface.

Effects of short-term gentle treadmill walking on subchondral bone in a rat model of instability-induced osteoarthritis

OBJECTIVEnSubchondral bone cyst (SBC) growth, caused by osteoclast activity during early knee osteoarthritis (OA) pathogenesis, should be treated to prevent further progressions of OA. In the present study, we evaluated the effects of gentle treadmill walking on subchondral bone and cartilage changes in an experimental rat model of destabilized medial meniscus (DMM).nnnMETHODnTwelve-week-old Wistar rats underwent DMM surgery in their right knee and sham surgery in their left knee and were assigned to either the sedentary group or walking group (n = 42/group). Animals in the walking group were subjected to treadmill exercise 2 days after surgery, which included walking for 12 m/min, 30 min/day, 5 days/week for 1, 2, and 4 week(s). Subchondral bone and cartilage changes were evaluated by micro-CT analysis, histological analysis, and biomechanical analysis.nnnRESULTSnTreadmill walking had a tendency to suppress SBC growth, which was confirmed by micro-CT (P = 0.06) and positive staining for tartrate-resistant acid phosphatase (TRAP) activity for the osteoclast number per bone surface (P = 0.09) 4 weeks after surgery. These changes coincide with the prevention of cartilage degeneration as evaluated by the Osteoarthritis Research Society International (OARSI) score (P < 0.05) and biomechanically softening (P < 0.05). Furthermore, treadmill walking could suppressed increasing osteocyte deaths (P < 0.01), which was positively correlated with the OARSI score (r = 0.77; P < 0.01).nnnCONCLUSIONnThese results indicate biomechanical and biological links exist between cartilage and subchondral bone; preventive effects of treadmill walking on subchondral bone deterioration might be partly explained by the chondroprotective effects.

Clinical Phenotype Classifications Based on Static Varus Alignment and Varus Thrust in Japanese Patients With Medial Knee Osteoarthritis.

To investigate the association between knee pain during gait and 4 clinical phenotypes based on static varus alignment and varus thrust in patients with medial knee osteoarthritis (OA).

Low-Intensity Pulsed Ultrasound Inhibits Messenger RNA Expression of Matrix Metalloproteinase-13 Induced by Interleukin-1β in Chondrocytes in an Intensity-Dependent Manner

The effect of low-intensity pulsed ultrasound (LIPUS) on articular cartilage metabolism has been characterized. However, the effect of LIPUS intensity on articular cartilage degradation factors remains unknown. This study aimed to investigate the immediate effect of LIPUS at several intensities on cultured chondrocytes treated with interleukin-1β (IL-1β) to induce an inflammatory response and on articular cartilage explants. Cultured chondrocytes and articular cartilage explants were treated by LIPUS at intensities of 0, 7.5, 30 and 120 mW/cm(2) or 0, 27 and 67 mW/cm(2), respectively. mRNA analysis revealed that LIPUS inhibited induction of MMP13 mRNA expression by 100 pg/mL IL-1β in cultured chondrocytes in an intensity-dependent manner. LIPUS also inhibited MMP13 and MMP1 mRNA expression in articular cartilage explants. Our results indicate that LIPUS may potentially protect articular cartilage by inhibiting MMP mRNA expression in an intensity-dependent manner and should thus be considered a useful candidate for daily treatment of OA.

The efficacy of a scaffold-free Bio 3D conduit developed from human fibroblasts on peripheral nerve regeneration in a rat sciatic nerve model

Background Although autologous nerve grafting is the gold standard treatment of peripheral nerve injuries, several alternative methods have been developed, including nerve conduits that use supportive cells. However, the seeding efficacy and viability of supportive cells injected in nerve grafts remain unclear. Here, we focused on a novel completely biological, tissue-engineered, scaffold-free conduit. Methods We developed six scaffold-free conduits from human normal dermal fibroblasts using a Bio 3D Printer. Twelve adult male rats with immune deficiency underwent mid-thigh-level transection of the right sciatic nerve. The resulting 5-mm nerve gap was bridged using 8-mm Bio 3D conduits (Bio 3D group, n = 6) and silicone tube (silicone group, n = 6). Several assessments were conducted to examine nerve regeneration eight weeks post-surgery. Results Kinematic analysis revealed that the toe angle to the metatarsal bone at the final segment of the swing phase was significantly higher in the Bio 3D group than the silicone group (-35.78 ± 10.68 versus -62.48 ± 6.15, respectively; p < 0.01). Electrophysiological studies revealed significantly higher compound muscle action potential in the Bio 3D group than the silicone group (53.60 ± 26.36% versus 2.93 ± 1.84%; p < 0.01). Histological and morphological studies revealed neural cell expression in all regions of the regenerated nerves and the presence of many well-myelinated axons in the Bio 3D group. The wet muscle weight of the tibialis anterior muscle was significantly higher in the Bio 3D group than the silicone group (0.544 ± 0.063 versus 0.396 ± 0.031, respectively; p < 0.01). Conclusions We confirmed that scaffold-free Bio 3D conduits composed entirely of fibroblast cells promote nerve regeneration in a rat sciatic nerve model.

Functional Movement Screen for Predicting Running Injuries in 18- to 24-Year-Old Competitive Male Runners.

Abstract Hotta, T, Nishiguchi, S, Fukutani, N, Tashiro, Y, Adachi, D, Morino, S, Shirooka, H, Nozaki, Y, Hirata, H, Yamaguchi, M, and Aoyama, T. Functional movement screen for predicting running injuries in 18- to 24-year-old competitive male runners. J Strength Cond Res 29(10): 2808–2815, 2015—The purpose of this study was to investigate whether the functional movement screen (FMS) could predict running injuries in competitive runners. Eighty-four competitive male runners (average age = 20.0 ± 1.1 years) participated. Each subject performed the FMS, which consisted of 7 movement tests (each score range: 0–3, total score range: 0–21), during the preseason. The incidence of running injuries (time lost because of injury ⩽ 4 weeks) was investigated through a follow-up survey during the 6-month season. Mann-Whitney U-tests were used to investigate which movement tests were significantly associated with running injuries. The receiver-operator characteristic (ROC) analysis was used to determine the cutoff. The mean FMS composite score was 14.1 ± 2.3. The ROC analysis determined the cutoff at 14/15 (sensitivity = 0.73, specificity = 0.54), suggesting that the composite score had a low predictability for running injuries. However, the total scores (0–6) from the deep squat (DS) and active straight leg raise (ASLR) tests (DS and ASLR), which were significant with the U-test, had relatively high predictability at the cutoff of 3/4 (sensitivity = 0.73, specificity = 0.74). Furthermore, the multivariate logistic regression analysis revealed that the DS and ASLR scores of ⩽3 significantly influenced the incidence of running injuries after adjusting for subjects characteristics (odds ratio = 9.7, 95% confidence interval = 2.1–44.4). Thus, the current study identified the DS and ASLR score as a more effective method than the composite score to screen the risk of running injuries in competitive male runners.