Publications by authors named "Ken Kadoya"

Background Context: Recent studies have demonstrated a close association between the development of ossification of the posterior longitudinal ligament (OPLL) and obesity. However, the association between OPLL and visceral fat obesity, which is prevalent in the Asian population, remains unexplored.

Purpose: To examine the impact of visceral fat obesity on the development of asymptomatic OPLL.

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Periprosthetic osteolysis is the primary cause of arthroplasty failure in the majority of patients. Mechanistically, wear debris released from the articulating surfaces of a prosthesis initiates local inflammation and several modes of regulated cell death programs, such as ferroptosis, which represents a promising therapeutic target in various chronic inflammatory diseases. Thus, the current study aimed at exploring the therapeutic potential of targeting ferroptosis in a polyethylene-wear-debris-induced osteolysis model.

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Background: Cartilage repair is a significant clinical challenge because of the limited intrinsic healing capacity. Current therapeutic strategies, such as cell transplantation therapy, aim to overcome this challenge by replacing damaged tissue with healthy cells. However, the long-term survival and functionality of transplanted cells remain major hurdles.

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The neurotrophic factor, Glial cell line derived neurotrophi factor (GDNF), exerts a variety of biological effects through binding to its receptors, GDNF family receptor alpha-1 (GFRα1), and RET. However, the existence of cells expressing GFRα1 but not RET raises the possibility that GFRα1 can function independently from RET. Here, it is shown that GFRα1 released from repair Schwann cells (RSCs) functions as a ligand in a GDNF-RET-independent manner to promote axon regeneration after peripheral nerve injury (PNI).

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Article Synopsis
  • Osteoarthritis (OA) is the most prevalent joint disease, involving cartilage breakdown and inflammation, with recent findings indicating that neutrophil extracellular vesicles (EVs) can help reduce inflammation and support cartilage health.
  • Research involved isolating these EVs from neutrophils under different conditions to analyze their effects on chondrocytes (cartilage cells) and the underlying molecular mechanisms through mouse models of OA.
  • The study revealed that EVs from neutrophils stimulated with TGF-β significantly inhibit harmful factors in chondrocytes, with the protein SFRP5 identified as a key player in these protective effects, suggesting potential avenues for OA treatment.
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Rheumatoid arthritis (RA) is a chronic systemic and autoimmune disease that primarily affects joints and causes pain, stiffness and swelling. The affected joints exhibit severe inflammation in the synovium and bone erosion, leading to joint deformity. Aging is an important factor facilitating the development of RA, as it is associated with an increase in the number of senescent cells and the production of the autoantibodies and proinflammatory cytokines in tissues.

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Given the potential fundamental function of osteal macrophages in bone pathophysiology, we study here their precise function in experimental osteoporosis. Gene profiling of osteal macrophages from ovariectomized mice demonstrated the upregulation of genes that were involved in oxidative stress, cell senescence, and apoptotic process. A single-cell RNA-Seq analysis revealed that osteal macrophages were heterogeneously clustered into 6 subsets that expressed proliferative, inflammatory, antiinflammatory, and efferocytosis gene signatures.

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  • Chronic compressive myelopathy (CCM) is a significant spinal cord issue in older adults, caused by pressure from bony or soft tissues, but no CT myelography method has been developed for rodents.
  • A new technique was created using a small syringe to inject a contrast medium into the subarachnoid space of anesthetized mice, allowing CT imaging to visualize the spinal cord shape in both healthy and affected mice.
  • This method is less invasive and quicker than traditional approaches, providing valuable images of the spinal cord, which can help in research on CCM and related spinal conditions in rodents.
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Introduction: Systemic osteogenesis has been speculated to be involved in the pathogenesis of ossification of the posterior longitudinal ligament (OPLL). Our purpose was to compare the radiologic prevalence and severity of heterotopic ossification in foot tendons of Japanese patients with OPLL and to determine their association with systemic heterotopic ossification.

Materials And Methods: Clinical and radiographic data of 114 patients with OPLL were collected from 2020 to 2022.

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Background Context: Recent studies suggest that ossification of the posterior longitudinal ligament (OPLL) is exacerbated by systemic metabolic disturbances, including obesity. However, although an increase in bone mineral density (BMD) measured at the lumbar spine has been reported in patients with OPLL, no studies have investigated the systemic BMD of patients with OPLL in detail.

Purpose: We investigated whether patients with OPLL develop increased whole-body BMD.

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  • The study investigates the link between dyslipidemia (abnormal lipid levels) and symptomatic ossification of the posterior longitudinal ligament (OPLL) in Japanese patients.
  • Data from 92 OPLL patients and 246 control participants were analyzed, revealing that dyslipidemia was significantly more common in those with OPLL.
  • The findings suggest that dyslipidemia, along with factors like age, body mass index (BMI), and diabetes, may contribute to the development of OPLL.
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Objective: The severity of osteoarthritis (OA) and cartilage degeneration is highly correlated with the development of synovitis, which is mediated by the activity of inflammatory macrophages. A better understanding of intercellular communication between inflammatory macrophages and chondrocytes should aid in the discovery of novel therapeutic targets. We undertook this study to explore the pathologic role of inflammatory macrophage extracellular vesicles (EVs) in cartilage degeneration.

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  • The study investigates the role of different fibroblast types in promoting neurite outgrowth after peripheral nerve injury.
  • Nerve-derived fibroblasts, particularly those from the epineurium, significantly enhance neurite growth compared to skin-derived fibroblasts, highlighting their unique regenerative properties.
  • Distinct molecular profiles of fibroblasts based on their nerve tissue location suggest that epineurium-derived fibroblasts are important for successful axon regeneration post-injury.
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Patients with ossification of the ligamentum flavum (OLF) in the lumbar spine may be at high risk of developing concomitant ossification of the entire spinal ligament, but the etiology remains unclear. We investigated the propensity for spinal ligament ossification in asymptomatic subjects with lumbar OLF using the data of 595 Japanese individuals receiving medical check-ups, including computed tomography (CT) scanning. The severity of OLF (total number of intervertebral segments with OLF) of the entire spine on CT was quantified using an OLF index.

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Although rodents have been widely used for experimental models of spinal cord diseases, the details of the growth curves of their spinal canal and spinal cord, as well as the molecular mechanism of the growth of adult rat spinal cords remain unavailable. They are particularly important when conducting the experiments of cervical spondylotic myelopathy (CSM), since the disease condition depends on the size of the spinal canal and the spinal cord. Thus, the purposes of the present study were to obtain accurate growth curves for the spinal canal and spinal cord in rats; to define the appropriate age in weeks for their use as a CSM model; and to propose a molecular mechanism of the growth of the adult spinal cord in rats.

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Although evidence has accumulated to indicate that Schwann cells (SCs) differentiate into repair SCs (RSCs) upon injury and that the unique phenotype of these cells allow them to provide support for peripheral nerve regeneration, the details of the RSCs are not fully understood. The findings of the current study indicate that the RSCs have enhanced adherent properties and a greater capability to promote neurite outgrowth and axon regeneration after peripheral nerve injury, compared to the non-RSCs. Further, transcriptome analyses have demonstrated that the molecular signature of the RSCs is distinctly different from that of the non-RSCs.

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Article Synopsis
  • The study focuses on the breakdown of the blood-brain spinal cord barrier (BBSCB) and its impact on central nervous system diseases, particularly spinal cord injury (SCI), highlighting the need for protective drugs.
  • Researchers developed a high-throughput screening assay (HTSA) to identify potential drugs and screened 1,570 existing medications, identifying three candidates: berberine, mubritinib, and pioglitazone.
  • The results showed that berberine and mubritinib effectively protected BBSCB function and reduced neuronal loss after SCI in mouse models, improving overall gait performance.
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Although inflammation is indispensable for the repair process in Wallerian degeneration (WD), the role of neutrophils in the WD repair process remains unclear. After peripheral nerve injury, neutrophils accumulate at the epineurium but not the parenchyma in the WD region because of the blood-nerve barrier. An increase or decrease in the number of neutrophils delayed or promoted macrophage infiltration from the epineurium into the parenchyma and the repair process in WD.

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There is currently no therapy available for periprosthetic osteolysis, the most common cause of arthroplasty failure. Here, the role of AnxA1 in periprosthetic osteolysis and potential therapeutics were investigated. Reducing the expression of AnxA1 in calvarial tissue was found to be associated with increased osteolytic lesions and the osteolytic lesions induced by debris implantation were more severe in AnxA1-defecient mice than in wild-type mice.

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Despite recent advancements in therapeutic options for disorders of the central nervous system (CNS), the lack of an efficient drug-delivery system (DDS) hampers their clinical application. We hypothesized that liposomes could be optimized for retrograde transport in axons as a DDS from peripheral tissues to the spinal cord and dorsal root ganglia (DRGs). Three types of liposomes consisting of DSPC, DSPC/POPC, or POPC in combination with cholesterol (Chol) and polyethylene glycol (PEG) lipid were administered to sciatic nerves or the tibialis anterior muscle of mature rats.

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  • Osteoarthritis (OA) is characterized by cartilage degeneration and joint stiffness, and its progression is linked to low-grade inflammation (LGI).
  • Recent studies highlight LGI's significant role as a contributor to OA, particularly in relation to obesity, aging, and metabolic syndromes, which are key risk factors.
  • Understanding how LGI and damage-associated molecular patterns (DAMPs) affect joint health could lead to new therapeutic strategies for OA by reducing inflammation and improving communication between joint cells.
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Accumulating evidences suggest that M2 macrophages are involved with repair processes in the nervous system. However, whether M2 macrophages can promote axon regeneration by directly stimulating axons nor its precise molecular mechanism remains elusive. Here, the current study demonstrated that typical M2 macrophages, which were generated by IL4 simulation, had the capacity to stimulate axonal growth by their direct effect on axons and that the graft of IL4 stimulated macrophages into the region of Wallerian degeneration enhanced axon regeneration and improved functional recovery after PNI.

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Background: Use of a wearable gait analysis system (WGAS) is becoming common when conducting gait analysis studies due to its versatility. At the same time, its versatility raises a concern about its accuracy, because its calculations rely on assumptions embedded in its algorithms. The purpose of the present study was to validate twenty spatiotemporal gait parameters calculated by the WGAS by comparison with simultaneous measurements taken with an optical motion capture system (OMCS).

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  • Double network hydrogels (DN gels) made from PAMPS and PDMA show promise as biomaterials for cartilage due to their biocompatibility and low toxicity.
  • Researchers generated micro-particles from DN gels to study how they influence biological reactions, particularly in macrophages and inflammation.
  • Findings indicate that these gel particles can activate macrophages, increase inflammation, and lead to local bone loss in mouse models, highlighting the need to address potential adverse reactions in artificial cartilage development.
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  • Bone is a flexible connective tissue essential for support, protection of organs, and mineral storage, undergoing constant remodeling to maintain its function.
  • Recent research highlights the immune system's role in this remodeling process, with chronic inflammation being a key factor that can lead to excessive bone loss.
  • Osteolytic diseases, caused by this imbalance, represent a major public health issue, prompting investigation into cellular mechanisms and treatment strategies for managing these conditions.
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