Biomedical subjects

Toru Yamaguchi

Publications and source records attributed to Toru Yamaguchi.

22 records · Page 2Linked to original sources

PubMed2002

Smad3 promotes alkaline phosphatase activity and mineralization of osteoblastic MC3T3-E1 cells.

Transforming growth factor (TGF) beta is abundantly stored in bone matrix and appears to regulate bone metabolism. Although the Smad family proteins are critical components of the TGF-beta signaling pathways, the roles of Smad3 in the expression of osteoblastic phenotypes remain poorly understood. Therefore, this study was performed to clarify the roles of Smad3 in the regulation of proliferation, expression of bone matrix proteins, and mineralization in osteoblasts by using mouse osteoblastic cell line MC3T3-E1 cells stably transfected with Smad3. Smad3 significantly inhibited [3H]thymidine incorporation and fluorescent intensity of the MTT-dye assay, compared with empty vector. Moreover, Smad3 increased the levels of type I procollagen, osteopontin (OPN), and matrix Gla protein (MGP) mRNA in Northern blotting. These effects of Smad3 mimicked the effects of TGF-beta on the same cells. On the other hand, Smad3 greatly enhanced ALP activity and mineralization of MC3T3-E1 cells compared with empty vector, although TGF-beta inhibited ALP activity and mineralization of wild-type MC3T3-E1 cells. A type I collagen synthesis inhibitor L-azetidine-2-carboxylic acid, as well as osteocalcin (OCN), significantly antagonized Smad3-stimulated ALP activity and mineralization of MC3T3-E1 cells. In conclusion, this study showed that in mouse osteoblastic cells, Smad3 inhibited proliferation, but it also enhanced ALP activity, mineralization, and the levels of bone matrix proteins such as type I collagen (COLI), OPN, and MGP. We propose that Smad3 plays an important role in osteoblastic bone formation and might help to elucidate the transcriptional mechanism of bone formation and possibly lead to the development of bone-forming drugs.

Alkaline Phosphatase↗

PubMed2002

Plasma lipids and osteoporosis in postmenopausal women.

Many clinical studies have shown that osteoporosis is associated with atherosclerosis and cardiovascular death. Although both high plasma levels of low density lipoprotein cholesterol (LDL-C) and low plasma levels of high density lipoprotein cholesterol (HDL-C) are known to be risk factors for atherosclerosis, it is unclear whether such lipid derangements are also associated with the pathogenesis of osteoporosis. In this study, we evaluated the relationships between plasma levels of total C, LDL-C, HDL-C, or triglyceride (TG) versus bone mineral density (BMD) at the lumbar spine, femoral neck, radius, or total body as well as the presence of vertebral fractures in 214 Japanese postmenopausal women (age range, 47-86 years, mean 62.7). Multiple regression analysis was performed between BMD at each skeletal site versus each lipid level adjusted for age, years after menopause, body mass index (BMI), and %fat. Plasma LDL-C levels were significantly and inversely correlated with the absolute values of both one-third radial (1/3R) and distal radial (UDR) BMD (p<0.01), and tended to be inversely correlated with the absolute values of L-BMD (p=0.051). In contrast, plasma HDL-C levels were significantly and positively correlated with the absolute values of L, 1/3R and UDR BMD (p<0.05). On the other hand, plasma TG levels were significantly lower in women with vertebral fractures than in those without fractures (97.0+/-36.5 vs. 126.4+/-65.8 mg/dl, mean+/-SD, p<0.05). When multivariate logistic regression analysis was performed with the presence of vertebral fractures as a dependent variable and each lipid level adjusted for age, years after menopause, BMI, and %fat as independent variables, TG alone was selected as an index affecting the presence of vertebral fractures (odds ratio: 0.51, 95% confidential interval: 0.29-0.89 per SD increase, p<0.05). Our study showed that plasma LDL-C and HDL-C levels were inversely and positively correlated with both R- and L-BMD values, respectively, while low plasma TG levels were associated with the presence of vertebral fractures in postmenopausal women. Thus, plasma lipids might be related to bone mass and bone fragility, and might be the common factor underlying both osteoporosis and atherosclerosis.

Aged↗

PubMed2002

[Osteoporosis and vascular calcification].

Many clinical studies have shown that osteoporosis is associated with atherosclerosis and cardiovascular death. Plasma lipids might be related to bone mass and bone fragility, and might be the common factor underlying both osteoporosis and atherosclerosis. It is interesting that statins, estrogens, and nitrogen-containing bisphosphonates have similar stimulatory effects on bone mass, because all of them are known to reduce LDL-cholesterol (C) and increase HDL-C in the plasma. Thus, these two disorders might be related to each other in terms of pathogenesis and therapeutic agents.

English Abstract↗

PubMedDate not supplied

Limb salvage treatment for congenital deficiency of the tibia.

Nine limb salvage treatments were performed in 7 patients with congenital deficiency of the tibia. All feet showed equinovarus deformity and were centralized in a slightly equinus position by placing the distal end of the fibula into the posterior facet of the calcaneus. Tibiofibular fusion was performed in 4 patients with partial deficiency, and fibular transfer (fibular centralization; Brown procedure) in 5 with complete deficiency of the tibia. Callus distraction lengthening was performed repeatedly for leg-length discrepancy on either the femur or the centralized fibula. Satisfactory functional and cosmetic results were obtained in all limbs with partial deficiency, whereas in limbs with completely deficiency, none of the 5 knees treated by fibular transfer achieved a satisfactory functional result because of insufficient quadriceps strength, progressive knee flexion contracture, and persistent ligamentous instability. Nevertheless, in these 5 cases, all patients were ultimately able to withstand weight-bearing.

Adolescent↗