Exploring the role of mechanical forces on tendon development using in vivo model: A scoping review.

Tendons transmit the muscle contraction forces to bones and drive joint movement throughout life. While extensive research have indicated the essentiality of mechanical forces on tendon development, a comprehensive understanding of the fundamental role of mechanical forces still needs to be impaerted. This scoping review aimed to summarize the current knowledge about the role of mechanical forces during the tendon developmental phase. The electronic database search using PubMed, performed in May 2023, yielded 651 articles, of which 16 met the prespecified inclusion criteria. We summarized and divided the methods to reduce the mechanical force into three groups: loss of muscle, muscle dysfunction, and weight-bearing regulation. In contrast, there were few studies to analyze the increased mechanical force model. Most studies suggested that mechanical force has some roles in tendon development in the embryo to postnatal phase. However, we identified species variability and methodological heterogeneity to modulate mechanical force. To establish a comprehensive understanding, methodological commonality to modulate the mechanical force is needed in this field. Additionally, summarizing chronological changes in developmental processes across animal species helps to understand the essence of developmental tendon mechanobiology. We expect that the findings summarized in the current review serve as a groundwork for future study in the fields of tendon developmantal biology and mechanobiology.

Effects of exercise on muscle reinnervation and plasticity of spinal circuits in rat sciatic nerve crush injury models with different numbers of crushes.

INTRODUCTION/AIMS: Motor function recovery is frequently poor after peripheral nerve injury. The effect of different numbers of nerve crushes and exercise on motor function recovery is unknown. We aimed to examine how different numbers of crushes of the rat sciatic nerve affects muscle reinnervation and plasticity of spinal circuits and the effect of exercise intervention. METHODS: Single and multiple sciatic nerve crush models with different numbers of crushes were created in rats. Treadmill exercise was performed at 10 m/min for 60 min, five times a week. Muscle reinnervation and synaptic changes in L4-5 motor neurons were examined by immunofluorescence staining. Behavioral tests were the sciatic functional index (SFI) and the pinprick tests. RESULTS: The percentage of soleus muscle reinnervation was not significantly increased by the presence of exercise in single or multiple crushes. Exercise after a single crush increased the contact of motor neurons with VGLUT1-containing structures (Exercised vs. Unexercised, 12.9% vs. 8.7%; p < .01), but after multiple crushes, it decreased with or without exercise (8.1% vs. 8.6%). Exercise after a single crush significantly improved SFI values from 14 to 24 days, and exercise after multiple crushes from 21 to 35 days (all p < .05). The pinprick test showed no difference in recovery depending on the number of crushes or whether or not exercised. DISCUSSION: Different numbers of sciatic nerve crushes affect muscle reinnervation and motor neuron synaptic changes differently, but motor function recovery may improve with exercise regardless of the number of crushes.

Influence of the site of injury on the spontaneous healing response in a rat model of total rupture of the anterior cruciate ligament.

AIM: The healing ability of the anterior cruciate ligament (ACL) injury is very poor; however, it has recently been shown to undergo self-healing with conservative treatments. In this study, we evaluated the influence of the site of injury on the healing process after complete transverse tear of ACL using a rat model. MATERIALS AND METHODS: A total of 58 skeletally mature Wistar rats were randomly assigned to various ACL injury groups: controlled abnormal movement-mid-portion (CAM-MP), controlled abnormal movement-femoral side (CAM-FS), ACL transection-mid-portion (ACLT-MP), or ACL transection-femoral side (ACLT-FS) injury groups. The ACL was completely transected in the mid-portion in the ACLT-MP and CAM-MP groups, and on the femoral side in the ACLT-FS and CAM-FS groups. Both CAM groups underwent extra-articular braking to control for abnormal tibial translation. The animals were allowed full cage activity until sacrifice postoperatively for histological and biomechanical assessment. RESULTS: Significant differences were found in the ratios of residual ligament lengths between the CAM-MP and CAM-FS groups, demonstrating the validity of each model. Spontaneous healing of the injured ACL was observed in the CAM-MP and CAM-FS groups but not in the ACLT-MP and ACLT-FS groups. The mechanical strength of the healing ACL did not differ between the CAM-MP and CAM-FS groups 8 weeks after injury; however, the former had better mechanical strength than the latter 12 weeks after the injury. CONCLUSION: ACL injuries in the mid-portion and on the femoral side may be treated with conservative therapy for spontaneous healing.

Evaluation of the Validity, Reliability, and Kinematic Characteristics of Multi-Segment Foot Models in Motion Capture.

This study aimed to evaluate the validity and reliability of our new multi-segment foot model by measuring a dummy foot, and examine the kinematic characteristics of our new multi-segment foot model by measuring the living body. Using our new model and the Rizzoli model, we conducted two experiments with a dummy foot that was moved within a range from -90 to 90 degrees in all planes; for the living body, 24 participants performed calf raises, gait, and drop jumps. Most three-dimensional (3D) rotation angles calculated according to our new models were strongly positively correlated with true values (r > 0.8, p < 0.01). Most 3D rotation angles had fixed biases; however, most of them were in the range of the limits of agreement. Temporal patterns of foot motion, such as those in the Rizzoli model, were observed in our new model during all dynamic tasks. We concluded that our new multi-segment foot model was valid for motion analysis and was useful for analyzing the foot motion using 3D motion capture during dynamic tasks.

Effects of controlled abnormal joint movement on the molecular biological response in intra-articular tissues during the acute phase of anterior cruciate ligament injury in a rat model.

BACKGROUND: The anterior cruciate ligament (ACL) is responsible for braking forward movement of the tibia relative to the femur and for tibial rotation. After ACL injury, this braking performance deteriorates, inducing abnormal joint movement. The purpose of this study was to clarify the effects of controlled abnormal joint movement on the molecular biological response in intra-articular tissues during the acute phase of ACL injury. METHODS: Eighty-four mature Wistar male rats were randomly assigned to a controlled abnormal movement (CAM) group, an ACL-transection (ACL-T) group, a sham-operated group, or an intact group. The ACL was completely transected at its midportion in the ACL-T and CAM groups, and a nylon suture was used to control abnormal tibial translation in the CAM group. The sham-operated group underwent skin and joint capsule incisions and tibial drilling without ACL transection. Animals were not restricted activity until sacrifice 1, 3, or 5 days after surgery for histological and gene expression assessments. Acute-phase inflammation requires an important balance between degenerative and biosynthetic processes and is controlled by the activities of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). Both types of gene were analyzed in this study. RESULTS: The ACL-T and CAM groups exhibited cleavage of the ACL at all time points. However, for the CAM group, the gap in the ligament stump was extremely small, and fibroblast proliferation was observed around the stump. Relative to the ACL-T group, the CAM group demonstrated significantly lower expression of MMP-13 mRNA and a lower MMP-13/TIMP-1 ratio on days 1 and 5 in the ACL, the medial meniscus and the lateral meniscus. The expression of TIMP-1 mRNA was not significantly different between the ACL-T and CAM groups. CONCLUSIONS: The study results suggested that controlling abnormal movement inhibited the inflammatory reaction in intra-articular tissues after ACL injury. This reaction was down-regulated in intra-articular tissues in the CAM group. Abnormal joint control caused prolonged inflammation and inhibited remodeling during the acute phase of ACL rupture.

Concurrent Joint Contact in Anterior Cruciate Ligament Injury induces cartilage micro-injury and subchondral bone sclerosis, resulting in knee osteoarthritis.

Objective: Anterior Cruciate Ligament (ACL) injury initiates post-traumatic osteoarthritis (PTOA) via two distinct processes: initial direct contact injury of the cartilage surface during ACL injury, and secondary joint instability due to the ACL deficiency. Using the well-established Compression-induced ACL rupture method (ACL-R) and a novel Non-Compression ACL-R model, we aimed to reveal the individual effects of cartilage compression and joint instability on PTOA progression after ACL injury in mice. Design: Twelve-week-old C57BL/6J male were randomly divided to three experimental groups: Compression ACL-R, Non-Compression ACL-R, and Intact. Following ACL injury, we performed joint laxity testing and microscopic analysis of the articular cartilage surface at 0 days, in vivo optical imaging of matrix-metalloproteinase (MMP) activity at 3 and 7 days, and histological and microCT analysis at 0, 7, 14, and 28 days. Results: The Compression ACL-R group exhibited a significant increase of cartilage roughness immediately after injury compared with the Non-Compression group. At 7 days, the Compression group exhibited increased MMP-induced fluorescence intensity and MMP-13 positive cell ratio of chondrocytes. Moreover, histological cartilage degeneration was observable in the Compression group at the same time point. Sclerosis of tibial subchondral bone in the Compression group was more significantly developed than in the Non-Compression group at 28 days. Conclusions: Both Compression and Non-Compression ACL injury initiated PTOA progression due to joint instability. However, joint contact during ACL rupture also caused initial micro-damage on the cartilage surface and initiated early MMP activity, which could accelerate PTOA progression compared to ACL injury without concurrent joint contact.

Sex differences in the kinematics and kinetics of the foot and plantar aponeurosis during drop-jump.

Plantar fasciitis is one of the most common musculoskeletal injuries in runners and jumpers, with a higher incidence in females. However, mechanisms underlying sex-associated differences in its incidence remain unclear. This study investigated the possible differences in landing and jumping kinematics and kinetics of the foot between sexes during drop-jump activities. Twenty-six participants, including 13 males and 13 females, performed drop-jumps from a platform onto force plates. Nineteen trials including ten males and nine females were selected for inverse dynamics analysis. The patterns of stretch and tensile force generated by the plantar aponeurosis (PA) were estimated using a multi-segment foot model incorporating the PA. Our results demonstrated that dorsiflexion, angular velocity, and normalized plantarflexion moment of the midtarsal joint right after the heel landed on the floor were significantly larger in females than in males. Consequently, the PA strain rate and tensile stress tended to be larger in females than in males. Such differences in the kinematics and kinetics of the foot and the PA between sexes could potentially lead to a higher prevalence of foot injuries such as plantar fasciitis in females.

Novel Multi-Segment Foot Model Incorporating Plantar Aponeurosis for Detailed Kinematic and Kinetic Analyses of the Foot With Application to Gait Studies.

Kinetic multi-segment foot models have been proposed to evaluate the forces and moments generated in the foot during walking based on inverse dynamics calculations. However, these models did not consider the plantar aponeurosis (PA) despite its potential importance in generation of the ground reaction forces and storage and release of mechanical energy. This study aimed to develop a novel multi-segment foot model incorporating the PA to better elucidate foot kinetics. The foot model comprised three segments: the phalanx, forefoot, and hindfoot. The PA was modeled using five linear springs connecting the origins and the insertions via intermediate points. To demonstrate the efficacy of the foot model, an inverse dynamic analysis of human gait was performed and how the inclusion of the PA model altered the estimated joint moments was examined. Ten healthy men walked along a walkway with two force plates placed in series close together. The attempts in which the participant placed his fore- and hindfoot on the front and rear force plates, respectively, were selected for inverse dynamic analysis. The stiffness and the natural length of each PA spring remain largely uncertain. Therefore, a sensitivity analysis was conducted to evaluate how the estimated joint moments were altered by the changes in the two parameters within a range reported by previous studies. The present model incorporating the PA predicted that 13%-45% of plantarflexion in the metatarsophalangeal (MTP) joint and 8%-29% of plantarflexion in the midtarsal joints were generated by the PA at the time of push-off during walking. The midtarsal joint generated positive work, whereas the MTP joint generated negative work in the late stance phase. The positive and negative work done by the two joints decreased, indicating that the PA contributed towards transfer of the energy absorbed at the MTP joint to generate positive work at the midtarsal joint during walking. Although validation is limited due to the difficulty associated with direct measurement of the PA force in vivo, the proposed novel foot model may serve as a useful tool to clarify the function and mechanical effects of the PA and the foot during dynamic movements.

Determination of relationship between foot arch, hindfoot, and hallux motion using Oxford foot model: Comparison between walking and running.

BACKGROUND: The foot arch plays an important role in propulsion and shock absorption during walking and running; however, the relationship among the foot arch, metatarsal locking theory, and nature of the windlass mechanism (WM) remain unclear. RESEARCH QUESTION: What are the differences in the kinematic relationship between the foot arch, hindfoot, and hallux during walking and running? METHODS: Relative angles within the foot were measured in 18 healthy men using the Oxford foot model (OFM). Data for barefoot walking at a comfortable speed and rearfoot running at 2.0 m/s were collected. Angles of the forefoot relative to the hindfoot (OFM-arch), hallux relative to the forefoot (Hallux) on the sagittal plane, and hindfoot relative to the shank (Hindfoot) on three anatomical planes were obtained. The medial longitudinal arch (MLA) angle was calculated to verify that OFM-arch can substitute the MLA angle. Each parameter was subjected to cross-correlation analysis and Wilcoxon signed-rank tests to examine the relationship with OFM-arch and compare them during walking and running. RESULT: OFM-arch was similar to the conventional MLA projection angle in both trials (gait: 0.79, running: 0.96 p < 0.01). Synchronization of the OFM-arch and Hallux angles was higher in running than in walking (gait: -0.09, running: -0.75 p < 0.01). Hindfoot supination was unrelated to OFM-arch. Hindfoot angle on the transverse plane exhibited a moderate relationship with OFM-arch, indicating different correlations in walking and running (gait: 0.63, running: -0.68 p < 0.01). SIGNIFICANCE: The elevation of the foot arch due to hallux dorsiflexion differed during walking and running; hence, other factors besides WM (such as intrinsic muscles) may affect the foot arch elevation during running. The hindfoot in the frontal plane does not contribute to arch raising and foot stability during running; it features different relationships with OFM-arch during walking and running.

Effect of Suppression of Rotational Joint Instability on Cartilage and Meniscus Degeneration in Mouse Osteoarthritis Model.

OBJECTIVE: Joint instability and meniscal dysfunction contribute to the onset and progression of knee osteoarthritis (OA). In the destabilization of the medial meniscus (DMM) model, secondary OA occurs due to the rotational instability and increases compressive stress resulting from the meniscal dysfunction. We created a new controlled abnormal tibial rotation (CATR) model that reduces the rotational instability that occurs in the DMM model. So, we aimed to investigate whether rotational instability affects articular cartilage degeneration using the DMM and CATR models, as confirmed using histology and immunohistochemistry. DESIGN: Twelve-week-old male mice were randomized into 3 groups: DMM group, CATR group, and INTACT group (right knee of the DMM group). After 8 and 12 weeks, we performed the tibial rotational test, safranin-O/fast green staining, and immunohistochemical staining for tumor necrosis factor (TNF)-α and metalloproteinase (MMP)-13. RESULTS: The rotational instability in the DMM group was significantly higher than that of the other groups. And articular cartilage degeneration was higher in the DMM group than in the other groups. However, meniscal degeneration was observed in both DMM and CATR groups. The TNF-α and MMP-13 positive cell rates in the articular cartilage of the CATR group were lower than those in the DMM group. CONCLUSIONS: We found that the articular cartilage degeneration was delayed by controlling the rotational instability caused by meniscal dysfunction. These findings suggest that suppression of rotational instability in the knee joint may be an effective therapeutic measure for preventing OA progression.

Structural and pathological changes in the enthesis are influenced by the muscle contraction type during exercise.

Mechanical stress is involved in the onset of sports-related enthesopathy. Although the amount of exercise undertaken is a recognized problem during disease onset, changes in muscle contraction type are also involved in the increase in mechanical stress during exercise. This study aimed to clarify the effects of increased mechanical stress associated with muscle contraction type and amount of exercise on enthesis. Twenty mice underwent treadmill exercise, and the muscle contraction type and overall load during exercise were adjusted by varying the angle and speed conditions. Histological analysis was used to the cross-sectional area of the muscle; area of the enthesis fibrocartilage (FC), and expression of inflammation-, degeneration-, and calcification-related factors in the FC area. In addition, the volume and structure of the bone and FC area were examined using microcomputer imaging. Molecular biological analysis was conducted to compare relative expression levels of inflammation and cytokine-related factors in tendons. The Overuse group, which increased the amount of exercise, showed no significant differences in parameters compared to the sedentary mice (Control group). The mice subjected to slow-speed downhill running (Misuse group) showed pathological changes compared to the Control and Overuse groups, despite the small amount of exercise. Thus, the enthesis FC area may be altered by local mechanical stress that would be increased by eccentric muscle contraction rather than by mechanical stress that increases with the overall amount of exercise. Clinical Significance: The muscle contraction type might be more involved in the onset of sports-related enthesopathy rather than the amount of exercise.

Effect of Various Types of Muscle Contraction with Different Running Conditions on Mouse Humerus Morphology.

How various types of muscle contraction during exercises affect bone formation remains unclear. This study aimed to determine how exercises with different muscle contraction types affect bone morphology. In total, 20 mice were used and divided into four groups: Control, Level, Down Slow, and Down. Different types of muscle contraction were induced by changing the running angle of the treadmill. After the intervention, micro-computed tomography (Micro-CT), tartrate-resistant acid phosphatase/alkaline phosphatase (ALP) staining, and immunohistochemical staining were used to analyze the humerus head, tendon-to-bone attachment, and humerus diaphyseal region. Micro-CT found that the volume ratio of the humeral head, the volume of the tendon-to-bone attachment region, and the area of the humeral diaphyseal region increased in the Down group. However, no difference was detected in bone morphology between the Level and Down Slow groups. In addition, histology showed activation of ALP in the subarticular subchondral region in the Down Slow and Down groups and the fibrocartilage region in the tendon-to-bone attachment. Moreover, Osterix increased predominantly in the Down Slow and Down groups.Overall bone morphological changes in the humerus occur only when overuse is added to EC-dominant activity. Furthermore, different type of muscle contractile activities might promote bone formation in a site-specific manner.

Impact of Controlling Abnormal Joint Movement on the Effectiveness of Subsequent Exercise Intervention in Mouse Models of Early Knee Osteoarthritis.

OBJECTIVE: Moderate mechanical stress is necessary for preserving the cartilage. The clinician empirically understands that prescribing only exercise will progress osteoarthritis (OA) for knee OA patients with abnormal joint movement. When prescribing exercise for OA, we hypothesized that degeneration of articular cartilage could be further prevented by combining interventions with the viewpoint of normalizing joint movement. DESIGN: Twelve-week-old ICR mice underwent anterior cruciate ligament transection (ACL-T) surgery in their right knee and divided into 4 groups: ACL-T, controlled abnormal joint movement (CAJM), ACL-T with exercise (ACL-T/Ex), CAJM with exercise (CAJM/Ex). Animals in the walking group were subjected to treadmill exercise 6 weeks after surgery, which included walking for 18 m/min, 30 min/d, 3 d/wk for 4 weeks. Joint instability was measured by anterior drawer test, and safranin-O staining and immunohistochemical staining were performed. RESULTS: OARSI (Osteoarthritis Research Society International) score of ACL-T/Ex group showed highest among 4 groups (P < 0.001). And CAJM/Ex group was lower than ACL-T/Ex group. Positive cell ratio of IL-1ß and MMP-13 in CAJM/Ex group was lower than ACL-T/Ex group (P < 0.05). CONCLUSIONS: We found that the state of the intra-articular environment can greatly influence the effect of exercise on cartilage degeneration, even if exercise is performed under the same conditions. In the CAJM/Ex group where joint movement was normalized, abnormal mechanical stress such as shear force and compression force accompanying ACL cutting was alleviated. These findings may highlight the need to consider an intervention to correct abnormal joint movement before prescribing physical exercise in the treatment of OA.

Basic locomotor muscle synergies used in land walking are finely tuned during underwater walking.

Underwater walking is one of the most common hydrotherapeutic exercises. Therefore, understanding muscular control during underwater walking is important for optimizing training regimens. The effects of the water environment on walking are mainly related to the hydrostatic and hydrodynamic theories of buoyancy and drag force. To date, muscular control during underwater walking has been investigated at the individual muscle level. However, it is recognized that the human nervous system modularly controls multiple muscles through muscle synergies, which are sets of muscles that work together. We found that the same set of muscle synergies was shared between the two walking tasks. However, some task-dependent modulation was found in the activation combination across muscles and temporal activation patterns of the muscle synergies. The results suggest that the human nervous system modulates activation of lower-limb muscles during water walking by finely tuning basic locomotor muscle synergies that are used during land walking to meet the biomechanical requirements for walking in the water environment.

Treadmill Exercise after Controlled Abnormal Joint Movement Inhibits Cartilage Degeneration and Synovitis.

Cartilage degeneration is the main pathological component of knee osteoarthritis (OA), but no effective treatment for its control exists. Although exercise can inhibit OA, the abnormal joint movement with knee OA must be managed to perform exercise. Our aims were to determine how controlling abnormal joint movement and treadmill exercise can suppress cartilage degeneration, to analyze the tissues surrounding articular cartilage, and to clarify the effect of treatment. Twelve-week-old ICR mice (n = 24) underwent anterior cruciate ligament transection (ACL-T) surgery on their right knees and were divided into three groups as follows: ACL-T, animals in the walking group subjected to ACL-T; controlled abnormal joint movement (CAJM), and CAJM with exercise (CAJM + Ex) (n = 8/group). Walking-group animals were subjected to treadmill exercise 6 weeks after surgery, including walking for 18 m/min, 30 min/day, 3 days/week for 8 weeks. Safranin-O staining, hematoxylin-eosin staining, and immunohistochemical staining were performed. The OARSI (Osteoarthritis research Society international) score was lower in the CAJM group than in the ACL-T group and was even lower in the CAJM + Ex group. The CAJM group had a lower meniscal injury score than the ACL-T group, and the CAJM + Ex group demonstrated a less severe synovitis than the ACL-T and CAJM groups. The observed difference in the perichondrium tissue damage score depending on the intervention method suggests different therapeutic effects, that normalizing joint motion can solve local problems in the knee joint, and that the anti-inflammatory effect of treadmill exercise can suppress cartilage degeneration.

Effects of Controlling Abnormal Joint Movement on Expression of MMP13 and TIMP-1 in Osteoarthritis.

OBJECTIVE: Abnormal joint movement is associated with osteoarthritis (OA). Previous studies using the controlling abnormal joint movement (CAJM) model of OA reported delayed cartilage degeneration; however, none of them focused on gait performance and the localization of matrix metalloproteinase 13 (MMP13) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in chondrocytes. Therefore, we aimed to investigate the effect of controlling abnormal joint movement on gait performance and the localization of MMP13 and TIMP-1, using kinematic and histological analyses. DESIGN: Rats were assigned to 2 groups: anterior cruciate ligament transection (ACL-T) group and CAJM group (n = 5/group); contralateral hind limbs of ACL-T rats were designated as intact. After 1, 2, and 4 weeks, step length was analyzed, and after 2, 4, and 8 weeks, Safranin O-Fast Green staining and immunohistochemical staining for MMP13 and TIMP-1 were performed. RESULTS: Step length did not differ significantly between the groups. However, degeneration of articular cartilage was higher in the ACL-T group than in the intact group (P < 0.05). There was no significant difference in the CAJM group at all time points. Immunohistochemical analysis of the MMP13/TIMP-1 relationship revealed a significant increase in the expression ratio of MMP13 after 4 weeks in the ACL-T group compared to the CAJM group (P < 0.05). CONCLUSIONS: Controlling abnormal joint movement may reduce mechanical stress owing to kinematic elements of small articulation including joint instability and delayed cartilage degeneration, despite the lack of kinematic change in step length.

Effects of exercise therapy on joint instability in patients with osteoarthritis of the knee: A systematic review.

Objective: Abnormal load stress caused by joint instability has been reported to be one of the factors responsible for the development of osteoarthritis (OA). However, few studies have investigated the efficacy of exercise therapy for patients with knee instability-induced OA, and there are no specific treatment guidelines or effects for this form of OA. Therefore, the purpose of this study was to examine the effect of exercise treatments for joint instability in patients with knee OA by a systematic review. Design: Systematic review. Results: Searches in three databases, PubMed, Cochrane, and the Physiotherapy Evidence Database, yielded 14 articles that were scrutinized, and 6 articles that met the inclusion criteria were selected. Conclusions: Exercise therapy focusing on joint instability, including muscle maintenance and strength training, and specific training targeting knee instability have no additional beneficial effects on knee joint instability. However, because of the benefits of treatment protocols based on patient attributes in exercise treatment focused on joint instability, it is necessary to investigate the effects in more detail in the future.

Adaptive changes in foot placement for split-belt treadmill walking in individuals with stroke.

BACKGROUND: Adaptation to split-belt treadmill walking differs between individual stroke survivors. Many discussions only address spatiotemporal parameters that are related to movement, and the changes in interlimb spatiotemporal parameters as a consequence of adaptation are poorly understood. OBJECTIVES: To investigate symmetry of the center of pressure (CoP) position relative to the center of mass (CoM), and ascertain whether this can be used to identify differences in adaptation of interlimb spatiotemporal parameters among stroke survivors during split-belt walking. METHODS: Twenty-two chronic post-stroke patients and nine elderly controls walked in tied- then split-belt (2:1 ratio of fast:slow) conditions. Spatiotemporal parameters were compared within groups to assess symmetry of the CoM-CoP angle at foot contact. RESULTS: Asymmetry of the CoM-CoP angle was associated with asymmetry of spatiotemporal parameters. Re-establishment of symmetry of CoM-CoP angle was reflected in re-established symmetry of spatiotemporal parameters in post-stroke and control participants. CONCLUSIONS: Post-stroke patients who re-establish symmetry of the COM-COP angle are able to adapt their walking for split-belt perturbation. This suggests that predictively symmetric foot placements on the fast and slow sides are necessary for adaptation in walking. Symmetrical foot placement is achieved by interlimb coordination and may contribute to dynamic stability.

Exercise enhances cognitive function and neurotrophin expression in the hippocampus accompanied by changes in epigenetic programming in senescence-accelerated mice.

Aerobic exercise is known to increase expression of neurotrophins, particularly brain-derived neurotrophic factor (BDNF), in the hippocampus and to improve cognitive function. Exercise exerts neuroprotective effects in the hippocampus by inducing epigenetic changes, which play crucial roles in aging and neurodegenerative diseases. Specifically, the activity levels of histone acetyltransferases (HATs) and histone deacetylases (HDACs) regulate histone acetylation and modulate gene transcription. The objective of the present study was to assess the interactive effects of exercise and aging on cognitive function, expression of neurotrophins (BDNF and neurotrophin-4) and their receptors (tyrosine receptor kinase B and p75), and epigenetic regulations, including the activity of HATs and HADCs in the hippocampus. We used the senescence-accelerated mouse (SAM) model, specifically 13-month-old SAM resistant 1(SAMR1) and SAM prone 1 (SAMP1) lines. Mice were distributed into four groups based on accelerated senescence and exercise status. Mice in the exercise groups exercised on a treadmill for approximately 60min a day, 5days a week. Aerobic exercise for 4 weeks improved cognitive function, accompanied by an increase in BDNF expression and a decrease in p75 transcription in both SAMR1 and SAMP1. In addition, the exercise regimen activated both HAT and HDAC in the hippocampus. Therefore, the present study reveals that despite accelerated senescence, long-term exercise improved cognitive function, upregulated the expression of BDNF, and downregulated p75, a receptor involved in apoptotic signaling. Furthermore, long-term exercise enhanced activity of both HAT and HDAC, which may contribute to the transcriptional regulation underlying the improvement of cognitive function.

Controlling Abnormal Joint Movement Inhibits Response of Osteophyte Formation.

Objective Osteoarthritis (OA) is induced by accumulated mechanical stress to joints; however, little has been reported regarding the cause among detailed mechanical stress on cartilage degeneration. This study investigated the influence of the control of abnormal joint movement induced by anterior cruciate ligament (ACL) injury in the articular cartilage. Design The animals were divided into 3 experimental groups: CAJM group ( n = 22: controlling abnormal joint movement), ACL-T group ( n = 22: ACL transection or knee anterior instability increased), and INTACT group ( n = 12: no surgery). After 2 and 4 weeks, the knees were harvested for digital microscopic observation, soft X-ray analysis, histological analysis, and synovial membrane molecular evaluation. Results The 4-week OARSI scores showed that cartilage degeneration was significantly inhibited in the CAJM group as compared with the ACL-T group ( P < 0.001). At 4 weeks, the osteophyte formation had also significantly increased in the ACL-T group ( P < 0.001). These results reflected the microscopic scoring and soft X-ray analysis findings at 4 weeks. Real-time synovial membrane polymerase chain reaction analysis for evaluation of the osteophyte formation-associated factors showed that the mRNA expression of BMP-2 and VEGF in the ACL-T group had significantly increased after 2 weeks. Conclusions Typically, abnormal mechanical stress induces osteophyte formation; however, our results demonstrated that CAJM group inhibited osteophyte formation. Therefore, controlling abnormal joint movement may be a beneficial precautionary measure for OA progression in the future.