Kozo Nakamura

We previously reported that fibroblast growth factor-2 (FGF-2) acts not only on osteoblasts to stimulate osteoclastic bone resorption indirectly but also on mature osteoclasts directly. In this study, we investigated the mechanism of this direct action of FGF-2 on mature osteoclasts using mouse and rabbit osteoclast culture systems. FGF-2 stimulated pit formation resorbed by isolated rabbit osteoclasts moderately from low concentrations (>/=10(-12) m), whereas at high concentrations ...

Schwann cells are the myelinating glia of the peripheral nervous system, and their development is regulated by various growth factors, such as neuregulin, platelet-derived growth factor (PDGF), and insulin-like growth factor-I (IGF-I). However, the mechanism of intracellular signaling pathways following these ligand stimuli in Schwann cell differentiation remains elusive. Here, we demonstrate that in cultured Schwann cells, neuregulin and PDGF suppressed the expression of ...

This study investigated the mechanism of direct and indirect actions of fibroblast growth factor 2 (FGF-2) on osteoclast differentiation using two mouse cell culture systems. In the coculture system of osteoblasts and bone marrow cells, FGF-2 stimulated osteoclast formation. This effect was decreased markedly by osteoprotegerin (OPG) or NS-398, a selective cyclo-oxygenase 2 (COX-2) inhibitor. FGF-2 (> or = 10(-9) M) stimulated receptor activator of nuclear factor kappaB ligand/osteoclast ...

Mechanical force or mechanical stress modulates intracellular signal pathways, including the mitogen-activated protein kinase (MAP kinase) cascades. In our system, cell stretching activated and cell contraction inactivated all three MAP kinase pathways (MKK1/2-extracellular signal-regulated kinase (ERK), MKK4 (SEK1)-cJun N-terminal kinase (JNK) and MKK3/6-p38 pathways). However, little is known about the molecular mechanisms that link the mechanical force to the MAP kinase cascades. To ...

This study aimed to estimate the prevalence of locomotive syndrome, sarcopenia, and frailty and clarify their co-existence in a population-based cohort. The third survey of Research on Osteoarthritis/Osteoporosis Against Disability (ROAD) study was conducted between 2012 and 2013, examining 963 subjects (aged ≥ 60 years; 321 men, 642 women). Locomotive syndrome, sarcopenia, and frailty were defined using three tests proposed by Japanese Orthopaedic Association, Asian Working Group for ...

Bone resorption is regulated by the immune system1,2, where T-cell expression of RANKL (receptor activator of nuclear factor (NF)-κB ligand), a member of the tumour-necrosis factor family that is essential for osteoclastogenesis, may contribute to pathological conditions, such as autoimmune arthritis3,4. However, whether activated T cells maintain bone homeostasis by counterbalancing the action of RANKL remains unknown. Here we show that T-cell production of interferon (IFN)-γ strongly ...

This study investigated the involvement of cell cycle factors in RANKL-induced osteoclast differentiation. Among the G1 cell cycle factors, Cdk6 was found to be a key molecule in determining the differentiation rate of osteoclasts as a downstream effector of the NF-kappaB signaling.

INTRODUCTION: A temporal arrest in the G1 phase of the cell cycle is a prerequisite for cell differentiation, making it possible that cell cycle factors regulate not only the proliferation but also the ...

The signaling through receptor tyrosine kinases expressed on mature osteoclasts has recently been suggested to be involved in osteoclastic bone resorption. This study investigated the mechanism and the possible physiological relevance of Gas6/Tyro 3, a receptor tyrosine kinase signaling pathway in osteoclasts in stimulating osteoclastic bone resorption using several mouse culture systems. Gas6, expressed ubiquitously in bone cells, did not affect the differentiation or the survival of ...

OBJECTIVE: To clarify the association between the occurrence and progression of knee osteoarthritis (KOA) with components of metabolic syndrome (MS), including overweight (OW), hypertension (HT), dyslipidaemia (DL), and impaired glucose tolerance (IGT), in a general population.

DESIGN: From the large-scale population-based cohort study entitled Research on Osteoarthritis/Osteoporosis Against Disability (ROAD) initiated in 2005, 1,690 participants (596 men, 1,094 women) residing in ...

A QCT-based nonlinear FEM was used to assess vertebral strength and mechanical parameters in postmenopausal women. It had higher discriminatory power for vertebral fracture than aBMD and vBMD. Alendronate effects were detected at 3 months, and marked bone density increases were noted in juxta-cortical areas compared to inner trabecular areas.IntroductionQCT-based finite element method (QCT/FEM) can predict vertebral compressive strength ex vivo. This study aimed to assess vertebral ...

OBJECTIVE: There is little information on falls by sex and age strata in Japan, and few factors associated with falls have been established. However, the association between bone and joint diseases and falls remains unclear. We examined prevalence of falls by sex and age strata, determined its association with radiographic osteoarthritis (OA) of the knee and lumbar spine, and determined knee and lower back pain after single and multiple falls.

METHODS: A questionnaire assessed the number ...

STUDY DESIGN: Retrospective multicenter study.

OBJECTIVE: To review the clinical characteristics of traumatic cervical spinal cord injury (SCI) associated with ossification of the posterior longitudinal ligament (OPLL).

SUMMARY OF BACKGROUND DATA: Despite its potentially devastating consequences, there is a lack of information about acute cervical SCI complicated by OPLL.

METHODS: This study included consecutive patients with acute traumatic cervical SCI (Frankel A, B, and C) who were ...

BACKGROUND: Clinical evidence demonstrating the effectiveness of pharmacological and mechanical thromboprophylaxis for the prevention of pulmonary embolism is limited because the prevalence of postoperative pulmonary embolism following total hip and knee arthroplasty is very low. Our purposes were to characterize a patient population with in-hospital pulmonary embolism, to identify perioperative risk factors associated with pulmonary embolism, and to analyze the effect of combining ...

Musculoskeletal diseases, especially osteoarthritis (OA) and osteoporosis (OP), impair activities of daily life (ADL) and quality of life (QOL) in the elderly. Although preventive strategies for these diseases are urgently required in an aging society, epidemiological data on these diseases are scant. To clarify the prevalence of knee osteoarthritis (KOA), lumbar spondylosis (LS), and osteoporosis (OP) in Japan, and estimate the number of people with these diseases, we started a ...

The role of Rac1 in osteoclast survival and bone-resorbing activity was examined using adenovirus vector expression systems. Rac1 is critically involved in M-CSF receptor signaling and mediates survival signaling primarily through PI3K/Akt pathways. Rac1 also plays a significant role in bone resorptive activity, probably by regulating the motility of osteoclasts.

INTRODUCTION: Rac1 is a member of Rho family small G-proteins, and recent studies have revealed that it mediates ...