Biomedical subjects

J P Bonjour

Publications and source records attributed to J P Bonjour.

At least 19 recordsLinked to original sources

PubMed2002

Survival and potential years of life lost after hip fracture in men and age-matched women.

Hip fracture is associated with a higher mortality rate in men than in women. However, mean age of men and women with hip fracture differs markedly. Thus, some of the differences in the clinical pattern and outcome between genders could be related to different ages. To avoid the influence of age on gender-specific outcome, we analyzed prefracture conditions and hip fracture outcome in a cohort of men and of age-matched women. Risk factors for low bone mass were recorded in 106 men (mean age +/- SD, 80.3 +/- 9.3 years) and 264 age-matched women (mean age 81.4 +/- 8.0) with hip fracture. We compared mortality rate, survival, years of potential life lost and modification of housing conditions. These outcomes were prospectively assessed during an average 3.6 years follow-up (up to 7 years). Men with hip fracture differed from age-matched hip-fractured women by a higher alcohol and tobacco consumption, a greater frequency of living in couple, and by less prevalent fractures. Mortality rate after hip fracture was significantly higher in men (RR = 1.74, 95% CI 1.34-2.24). Since mortality is higher in the general male population, we compared reduction in life expectancy taking into account the gender-specific mortality rate. The excess mortality in each age-group of hip-fractured patients, which was measured during the whole follow-up period, and is an estimate of death attributable to fracture, did not differ between genders. Reduction in life expectancy due to hip fracture was similar in both genders (5.9 +/- 4.5 and 5.8 +/- 4.8 years, in men and women, respectively; NS), but the proportion of the years of life lost was higher in men (70 +/- 33%) than in women (59 +/- 42%, p < 0.01). It was concluded that for the same age, mortality rate after hip fracture was higher in men than in women. Although the reduction in life expectancy was similar in both genders, the proportion of the years of life lost was higher in men, suggesting a worse impact of hip fracture on survival in men, even after consideration of the higher mortality rate in the general male population.

Aged↗

PubMed2002

Evidence for a role of p38 MAP kinase in expression of alkaline phosphatase during osteoblastic cell differentiation.

In the present study, we investigate the implication of the mitogen-activated protein kinases (MAPKs) Erk, p38, and JNK in mediating the effect of fetal calf serum (FCS) on the differentiation of MC3T3-E1 osteoblast-like cells. Erk is stimulated by FCS in proliferating, early-differentiating, as well as in mature cells. Activation of p38 by FCS is not detected in proliferating cells but is observed as the cells differentiate. JNK is activated in response to FCS throughout the entire differentiation process, but a maximal stimulation is observed in early differentiating cells. The roles of Erk and p38 pathways in mediating MC3T3-E1 cell differentiation was determined using specific inhibitors such as U0126 and SB203580, respectively. These experiments confirmed that the Erk pathway is essential for mediating cell proliferation in response to FCS, but indicated that this MAP kinase has little effect in regulating the differentiation of MC3T3-E1 cells. In contrast, p38 only marginally influenced proliferation, but appeared to be critical for the control of alkaline phosphatase (ALP) expression in differentiating cells. Finally, results obtained with high doses of SB203580, which also affected JNK activity, suggest that p38 and/or JNK are probably also involved in the control of type 1 collagen and osteocalcin expression in differentiating cells. The data indicate that MAPKs regulate different stages of MC3T3-E1 cell development in response to FCS. Distinct MAPK pathways seem to independently modulate osteoblastic cell proliferation and differentiation, with Erk playing an essential role in cell replication, whereas p38 is involved in the regulation of ALP expression during osteoblastic cell differentiation. JNK is also probably involved in the regulation of osteoblastic cell differentiation, but its precise role requires further investigation.

3T3 Cells↗

PubMed2002

Recovery of proximal tibia bone mineral density and strength, but not cancellous bone architecture, after long-term bisphosphonate or selective estrogen receptor modulator therapy in aged rats.

Various bisphosphonates and the selective estrogen receptor modulator (SERM) raloxifene are approved treatments of postmenopausal osteoporosis. They increase bone mineral density (BMD), decrease bone turnover, and reduce vertebral fracture incidence through different cellular mechanisms. We investigated the bone cellular activities, architecture, mineral content/density, and strength of ovariectomized (ovx) rats on a long-term bisphosphonate or SERM treatment, at doses of either agent correcting bone strength. Eleven weeks postovariectomy, 6-month-old rats were treated with the SERM MDL 103,323 or with the bisphosphonate pamidronate for 5 months. Doses of pamidronate and MDL 103,323 were selected from previous studies showing correction of the ovx-induced decrease of ultimate strength of proximal tibia. Ultimate and yield strengths, BMD, and histomorphometric parameters were all quantified at the same site, i.e., the proximal tibia metaphysis. Long-term pamidronate decreases bone turnover and bone formation activity, leading to trabecular thinning. MDL 103,323 decreases bone turnover to a lesser extent, and slightly protects trabecular architecture by uncoupling bone resorption and formation activities. The yield strength is corrected by pamidronate, but not by MDL 103,323 treatment. However, neither compound restores the ovariectomy-induced cancellous bone loss. Total tissue area and cortical thickness are unchanged with pamidronate or MDL 103,323 treatment, indicating that cortical bone mass, thickness, and cross-sectional area are not modified. The discrepancy between proximal tibia BMD and mechanical resistance to fracture modifications, on the one hand, and cancellous bone volume, on the other hand, could be due to changes in the degree of mineralization of bone matrix and/or of the intrinsic properties of the bone matrix.

Aging↗

PubMed2002

Dietary essential amino acid supplements increase bone strength by influencing bone mass and bone microarchitecture in ovariectomized adult rats fed an isocaloric low-protein diet.

This study was designed to investigate whether the administration of dietary essential amino acid supplements in adult rats made osteoporotic by estrogen deficiency and reduced protein intake could reverse the deleterious effects caused by these maneuvers. This animal model was selected to mimic the situation observed in elderly women in whom estrogen deficiency and/or low-protein intake (but also calcium and vitamin D deficiency) are known to contribute to the pathogenesis of osteoporosis. Six-month-old rats were ovariectomized (OVX) and fed an isocaloric 2.5% casein diet for 10 weeks or sham-operated (SHAM) and fed an isocaloric 15% casein diet. The animals fed the 2.5% casein diet were given isocaloric supplements of essential amino acids in similar relative proportion to that of casein at doses of 2.5% or 5% of total diet for an additional 16 weeks. Vertebrae, femur, and tibia bone mineral density (BMD); ultimate strength; and microtomographic histomorphometry were evaluated before and after dietary essential amino acid supplements. Essential amino acid supplements increased vertebrae, femur, and tibia bone strength in OVX rats fed a low-protein diet. The mechanical changes induced by this dietary isocaloric supplement were associated with the prevention of a further BMD decrease or even with some increases and changes in microarchitecture such as from a rod to a plate trabecular spacial configuration and increased cortical thickness. Higher insulin-like growth factor (IGF) I levels, as well as greater bone formation and reduced bone resorption as assessed by biochemical markers of bone remodeling, were found in rats receiving essential amino acid supplements. In conclusion, dietary essential amino acid supplements increased bone strength through modifications of BMD, trabecular architecture, and cortical thickness possibly by an IGF-I-mediated process.

Amino Acids, Essential↗

PubMed2001

Species-specific mechanisms control the activity of the Pit1/PIT1 phosphate transporter gene promoter in mouse and human.

The Pit1 phosphate transporter is involved in regulated phosphate handling in bone forming cells. In this study, we compared the structure of the murine and human Pit1/PIT1 promoters and characterized cis-acting elements controlling Pit1/PIT1 expression. The Pit1/PIT1 promoter sequence and its location relative to the first transcribed exon are conserved and similar transcription factor binding sites are found at identical positions in mouse and human. Luciferase reporter gene assays in transiently transfected mouse ATDC5 chondrocytes and human SaOS-2 osteoblasts indicated that the activity of the mouse Pit1 promoter depends on several cis-acting elements, including ATF/CREB, Sp1 and AP-1 sites, an E-box and a TATA box. In contrast, the activity of the human promoter essentially requires a TATA-like sequence and one single Sp1 site. This Sp1 site binds Sp1, Sp3, as well as unidentified proteins present in SaOS-2 nuclear extracts and co-transfection experiments in SL2 cells indicate that Sp1 and Sp3 activate transcription from the human PIT1 promoter. These data suggest that, despite similarities in promoter structure, changes in the relative importance of conserved transcription factor binding sites cause species-dependent differences in Pit1 promoter function, which allow Sp1-related proteins to play a particularly important role in human.

5' Flanking Region↗

PubMed2001

Gain in bone mineral mass in prepubertal girls 3.5 years after discontinuation of calcium supplementation: a follow-up study.

BACKGROUND: Calcium supplementation during childhood and adolescence increases bone-mass accrual. Whether or not this benefit persists after discontinuation of supplementation is not known. We previously showed a favourable effect of milk-extracted calcium phosphate incorporated in various foods on accumulation of bone mineral mass in 8-year-old girls. We now report the results of a follow-up study undertaken more than 3 years after the end of calcium supplementation. METHODS: Anthropometric and bone variables were measured in 116 of the 144 girls whose data had been studied at the end of the supplementation period. The mean time elapsed between the end of the intervention period and this follow-up measurement was 3.5 years. Areal bone mineral density was measured by dual-energy X-ray absorptiometry at the same six skeletal sites as those studied during the intervention phase. FINDINGS: We were able to remeasure 62 and 54 girls of the calcium-supplemented and placebo groups, respectively. The increase from baseline in the overall mean bone mineral density of the six skeletal sites was still highly significant (calcium-supplemented group 179 mg/cm(2) [SE 8] vs placebo group 151 mg/cm(2) [7], p=0.012). A significant difference in favour of the supplemented group was also seen with respect to mean bone mineral content (p=0.031) and mean bone area (p=0.04). Difference in pubertal maturation did not seem to account for the recorded differences. INTERPRETATION: Our results suggest that this form of milk-extracted calcium phosphate taken during the prepubertal period can modify the trajectory of bone mass growth and cause a long-standing increase in bone mass accrual, which lasts beyond the end of supplementation.

Absorptiometry, Photon↗

PubMed2001

Allogeneic bone marrow transplantation is associated with a preferential femoral neck bone loss.

Osteoporosis is a major complication of organ transplantation. Little is known about the risk of developing osteoporosis in bone marrow transplant (BMT) recipients. We studied early and late changes in bone mineral density (BMD), as well as biochemical markers of bone remodeling, in patients at the time of allogeneic BMT (alloBMT) and up to 13 years thereafter. In a cross-sectional study, 102 patients (40 women, 62 men, mean age +/- SEM, 38.9 +/- 1.6 years) were segregated into a first group (A, n = 48) and evaluated before or during the first weeks (mean +/- SD 0.3 +/- 0.1 month, range -0.5 to 3 months) following alloBMT, and a second group (B, n = 54) studied 60.1 +/- 5.6 months (range 6-156 months) following alloBMT. Lumbar spine (LS) BMD was similar in groups A and B and was within normal limits. In contrast, femoral neck (FN) Z- and T-scores were significantly decreased in group B compared with group A (-0.68 +/- 0.14 vs -0.03 +/- 0.14 SD and -0.84 +/- 0.14 vs -0.22 +/- 0.14 SD, respectively; p < or = 0.002). Osteopenia (T-score between -1 and -2.5 SD) was present in 35% of group A and 43% of group B patients (NS). Osteoporosis (T-score < -2.5 SD) was detected in 7% of group B patients, but in none of those in group A (p = 0.05). In a longitudinal study, 56 subjects were evaluated at the time of alloBMT, and 33 and 23 were studied 6 or 12 months later, respectively (13 women, 20 men, 37.5 +/- 1.6 years). All were treated with supplements of calcium and vitamin D. Amenorrheic women received hormone replacement therapy (HRT). Three-monthly pamidronate infusions were given to 15 men and 10 non-amenorrheic women who were osteopenic/osteoporotic or had elevated baseline bone turnover markers. Mean baseline LS and FN Z- and T-scores were within normal range. Six months after BMT, FN BMD decreased by 4.2 +/- 0.7% (p < 0.001), and whole body BMD and bone mineral content by 1.5 +/- 0.4% and 3.1 +/- 0.6%, respectively (p < or = 0.0001). Twelve months after the graft, there was no further significant bone loss and only FN BMD decrease remained significantly different compared with baseline (-5.6 +/- 1.1%, p < or = 0.0001). These results indicate that the risk of decreased BMD is higher for the femoral neck than the lumbar spine and whole body levels in patients with allogeneic bone marrow transplantation, and that bone loss occurs mainly during the first 6 months after the graft.

Adolescent↗

PubMed2001

Protein intake and bone disorders in the elderly.

Malnutrition, most notably protein deficiency, contributes to the occurrence of osteoporotic fractures not only by decreasing bone mass but also by altering muscle function. Furthermore, malnutrition is associated with increased morbidity in patients with osteoporotic fractures. The somatomedin system (IGF-1) may be directly involved in the pathogenesis of osteoporotic hip fractures and their complications in elderly patients. A low IGF-1 level is a risk factor for hip fracture. In subjects with appropriate intakes of vitamin D and calcium, giving protein supplements to correct an inadequate spontaneous protein intake increases circulating IGF-1 levels, improves clinical outcomes after hip fracture, and prevents bone mineral density loss at the proximal femur. Supplemental protein also significantly reduces the length of inpatient rehabilitation care. These data emphasize the importance of adequate nutrient intake in the prevention and treatment of osteoporotic fractures.

Age Distribution↗

PubMed2001

Stimulation of sodium-dependent inorganic phosphate transport by activation of Gi/o-protein-coupled receptors by epinephrine in MC3T3-E1 osteoblast-like cells.

Recent data have shown that activation of Gi-protein-coupled receptors in osteoblast-like cells enhances the proliferation and differentiation of these cells. In the present study, we investigated the effect of epinephrine, an agonist of Gi-protein-coupled receptors in MC3T3-E1 cells, on Pi transport, type III Pi transporter expression, and the signaling mechanism(s) involved in this response. Epinephrine time- and dose-dependently stimulated sodium-dependent Pi transport and this effect was dependent on RNA and protein synthesis. This effect was associated with a related time-dependent increase in Pit-1 mRNA expression. Kinetic analysis indicated that the change in Pi transport activity induced by epinephrine was due to alteration in the maximal rate of Pi transport. Investigation of Pi transport stimulation by several adrenergic agonists and its inhibition by spiperone suggest that the effect of epinephrine on Pi transport was mediated by alpha1-adrenergic receptors. Pertussis toxin, which inactivates Gi/o proteins, significantly blunted the stimulatory effect of epinephrine on Pi transport. Analysis of the signaling pathways involved in this response has suggested a major role of protein kinase C and a small contribution from the mitogen-activated protein kinase Erk (MAPK(erk)). The results show that, in MC3T3-E1 osteoblast-like cells, activation of Gi/o-protein-coupled receptors induces stimulation of Pi transport. This effect is mediated by activation of protein kinase C and the MAPK(erk) pathway and probably involves the synthesis of Pit-1 transporters.

3T3 Cells↗

PubMed2001

Lower femoral neck bone mineral density in prepubertal former preterm girls.

The purpose of this case-control study was to determine bone mineral content and areal bone mineral density at various skeletal sites in former preterm girls, aged 7-9 years, and to compare these data with age-matched term controls. Subjects included 25 white, prepubertal, former preterm girls (gestational age 30.8 +/- 0.3 weeks, birthweight 1461 +/- 56 g [mean +/- SEM]). Controls included 50 healthy, white, prepubertal girls born at term and matched for age (two controls per case). Measurements included anthropometric variables, calcium intake according to a food-frequency questionnaire, bone mineral content (BMC; grams), and areal bone mineral density (aBMD; grams per square centimeter), using dual-energy X-ray absorptiometry (DXA) at six skeletal sites. Thirteen preterm girls and 13 age-matched term controls were reassessed 1 year after the first DXA measurement. The former preterm girls were similar to controls in terms of age and height, but were lighter (24.6 +/- 0.6 vs. 27.0 +/- 0.6 kg, p = 0.02). They also reported a higher median calcium intake (1058 vs. 759 mg/day, p = 0.004). aBMD was lower in former preterms compared with controls at the level of the radial metaphysis (0.283 +/- 0.006 vs. 0.298 +/- 0.004, p = 0.04), femoral neck (0.593 +/- 0.011 vs. 0.638 +/- 0.010, p = 0.007), and total hip (0.596 +/- 0.012 vs. 0.640 +/- 0.010, p = 0.007), but was similar between the two groups at the radial diaphysis (0.437 +/- 0.004 vs. 0.436 +/- 0.004) and femoral diaphysis (1.026 +/- 0.015 vs. 1.030 +/- 0.011). Femoral neck aBMD remained lower compared with controls in the subgroup of preterm girls reassessed after 1 year (0.608 +/- 0.017 vs. 0.672 +/- 0.020, p = 0.02). In random effects models for longitudinal data, taking into account the effects of age, weight, and height on aBMD (dependent variable), femoral neck aBMD remained lower in former preterms (p < 0.001). Prepubertal former preterm girls showed growth recovery, but had lower aBMD at the hip and radial metaphysis than age-matched term controls, despite spontaneously higher calcium intake. Preterm girls had similar aBMD results compared with controls at sites with predominantly cortical bone (radial and femoral diaphysis), which are known to be more sensitive to calcium intake.

Bone Density↗

PubMed2001

Oligo-amenorrheic long-distance runners may lose more bone in spine than in femur.

PURPOSE: Strenuous training can be associated with amenorrhea leading to amenorrhea-related accelerated bone loss. Insufficient calorie energy, calcium, and/or protein intakes can also be frequently encountered in women with intense training, possibly contributing to bone loss. Long-distance runners with or without regular menses (age range 19-37 yr) were prospectively studied. METHODS: Changes in areal bone mineral density (BMD) were measured at 1-yr interval. RESULTS: Among 10 eumenorrheic, 11 oligo-amenorrheic, and 9 oral contraceptive users, there was no difference in energy, calcium, or protein intakes. Baseline BMD values were significantly lower in the oligo-amenorrheic group than in the two others at the level of lumbar spine (anteroposterior view: 0.941+/-0.039 in oligo-amenorrheic vs 1.077+/-0.029 or 1.051 +/-0.017 g x cm(-2), P < 0.005, in the eumenorrheic and contraceptive user groups, respectively) but not in weight-bearing bone such as proximal and midshaft femur. Over a 1-yr interval, during which the three groups did not differ in terms of running distances and dietary intakes, oligo-amenorrheic women displayed a significant decrease in lumbar spine BMD in lateral view (-0.049+/-0.012 in oligo-amenorrheic vs -0.001+/-0.013 and 0.014+/-0.012 g x cm(-2), p < 0.005, in the eumenorrheic and contraceptive user groups, respectively). We did not detect any significant change in femoral neck, trochanter, or midshaft BMD. CONCLUSIONS: Oligo-amenorrhea in long-distance runners, with adequate dietary intakes, was associated with a decrease in BMD affecting more the lumbar spine than the proximal and midshaft femur during a 1-yr follow-up.

Adult↗

PubMed2001

Protein intake and bone growth.

Among osteotrophic nutrients, proteins play an important role in bone development, thereby influencing peak bone mass. Consequently, protein malnutrition during development can increase the risk of osteoporosis and of fragility fracture later in life. Both animal and human studies indicate that low protein intake can be detrimental for both the acquisition of bone mass during growth and its conservation during adulthood. Low protein intake impairs both the production and action of IGF-I (Insulin-like growth factor-I). IGF-I is an essential factor for bone longitudinal growth, as it stimulates proliferation and differentiation of chondrocytes in the epiphyseal plate, and also for bone formation. It can be considered as a key factor in the adjustments of calcium-phosphate metabolism required for normal skeletal development and bone mineralization during growth. In healthy children and adolescents, a positive association between the amount of ingested proteins and bone mass gain was observed in both sexes at the level of the lumbar spine, the proximal femur and the midfemoral shaft. This association appears to be particularly significant in prepubertal children. This suggests that, like for the bone response to either the intake of calcium or weight-bearing exercise, the skeleton would be particularly responsive to the protein intake during the years preceding the onset of pubertal maturation.

Animals↗

PubMed2001

Osteoporosis, genetics and hormones.

Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue. At a given age, bone mass results from the amount of bone acquired during growth, i.e. the peak bone mass (Bonjour et al., 1991, Theintz et al. 1992) minus the age-related bone loss which particularly accelerates after menopause. The rate and magnitude of bone mass gain during the pubertal years and of bone loss in later life may markedly differ from one skeletal site to another, as well as from one individual to another. Bone mass gain is mainly related to increases in bone size, that is in bone external dimensions, with minimal changes in bone microarchitecture. In contrast, postmenopausal and age-related decreases in bone mass result from thinning of both cortices and trabeculae, from perforation and eventually disappearance of the latter, leading to significant alterations of the bone microarchitecture (Fig. 1).

Bone Density↗

PubMed2000

Evaluation of hormone replacement therapy use by the sales figures.

Despite the efficiency of hormone replacement therapy (HRT) to prevent climacteric manifestations and possibly the long-term deleterious influences of menopause, the prevalence of HRT is relatively low, and quite variable, depending on the population studied. Presently, there is no information regarding HRT in Switzerland and in the region of Geneva, which have particularly aged populations, with a life expectancy among the longest in the Western world. In this study, the number of women treated per year in 1993 and 1996, as well as the prevalence of HRT were estimated, based on the total amount of hormone preparations sold for HRT. In Switzerland, for a female population older than 45 years of about 1.45 million, the number of women on HRT was approximately 166,000 in 1993 and 202,000 in 1996. For Geneva, the female population was more than 86,000, and the number of treated women was about 14,000 and 21,000 in 1993 and 1996, respectively. Depending on the age class considered as susceptible of receiving HRT, the prevalence of this therapy may vary between 15 and 20% for Switzerland, and between 21 and 27% for Geneva in 1993. It was estimated between 17 and 24%, and 31 and 41% in 1996. These values are quite comparable to those reported for other countries with a similar socioeconomic level and obtained using different methods of evaluation.

Age Factors↗

PubMed2000

A novel in vitro culture system for analysis of functional role of phosphate transport in endochondral ossification.

In vivo expression of the type III sodium-dependent phosphate transporter (NaPiT) Glvr-1 during endochondral ossification, suggests a functional role for inorganic phosphate (Pi) transport in cartilage calcification. For further analysis of this relationship, an in vitro model of endochondral ossification is required. In this context, we investigated the characteristics of Pi transport in the new chondrogenic cell line ATDC5 in relation to extracellular matrix (ECM) formation and mineralization. Pi uptake in ATDC-5 cells and in isolated matrix vesicles (MVs) is mediated by an Na-dependent Pi transporter with a pH dependency characteristic of a type III Pi carrier (lower activity at alkaline pH). Northern blot analysis indicated that ATDC-5 cells express Glvr-1 transcripts during the various stages of their maturation with a maximal level during the proliferating stage. In isolated MVs, Pi transport activity was maximal at day 21, concomitant with the beginning of type X collagen messenger RNA expression. These events preceded the initiation of matrix mineralization, which was apparent at day 25, and then gradually increased until day 47. This temporal relationship between maximal Pi transport activity in MVs and the expression of a marker of mineralizing chondrocytes is compatible with the possible involvement of Pi transport in the ECM calcification observed in ATDC-5 cell cultures. In conclusion, these observations suggest that ATCD-5 cells in culture represent a promising model for the analysis of a functional role of Pi transport in the initial events of endochondral ossification.

Biological Transport↗

PubMed2000

Transforming growth factor-beta stimulates inorganic phosphate transport and expression of the type III phosphate transporter Glvr-1 in chondrogenic ATDC5 cells.

Members of the transforming growth factor (TGF)-beta family are important regulators of skeletal development. In this study, we investigated the effect of TGF-beta1 on inorganic phosphate (Pi) transport and on expression of the type III Pi carriers Glvr-1 and Ram-1 in murine ATDC5 chondrocytes. TGF-beta1 induced a selective, dose- and time-dependent increase in sodium-dependent Pi transport in ATDC5 cells. This response was dependent on RNA and protein synthesis and reflected a change in the maximal rate of the transport system, suggesting that TGF-beta1 induces the synthesis of new Pi carriers and their insertion into the plasma membrane. Consistently, Northern blotting analysis showed a dose-dependent increase in Glvr-1 messenger RNA expression in response to TGF-beta1, which preceded the maximal stimulation of Pi transport by several hours. Glvr-1 thus likely mediates at least part of the increase in Pi uptake induced by TGF-beta1. Ram-1 messenger RNA expression was not affected by TGF-beta1. TGF-beta1 activated the Smad signaling pathway and the mitogen-activated protein kinases ERK and p38 in ATDC5 cells. Unlike the regulation of Pi transport by receptor tyrosine kinase agonists in osteoblasts, the effect of TGF-beta1 on Pi uptake in ATDC5 cells did not involve protein kinase C or mitogen-activated protein kinases, suggesting that a specific, possibly Smad-dependent, signal mediates this response. In conclusion, TGF-beta1 stimulates Pi transport and Glvr-1 expression in chondrocytes, suggesting that, like proliferation, differentiation, and matrix synthesis, Pi handling is subject to regulation by TGF-beta3 family members in bone-forming cells.

Animals↗

PubMed2000

Dietary protein restriction lowers plasma insulin-like growth factor I (IGF-I), impairs cortical bone formation, and induces osteoblastic resistance to IGF-I in adult female rats.

Dietary protein deficiency, common in elderly, is associated with decreased areal bone mineral density and plasma insulin-like growth factor I (IGF-I). To investigate the early adaptation of bone cells to protein restriction, 6-month-old female rats were pair-fed with isocaloric 15% (control) or 2.5% casein diets for 14 days. Animals were then treated daily with rhIGF-I/IGFBP-3 (1:4, 2.5 mg IGF-I/kg BW) or with vehicle for 10 days. After double-labeling, proximal metaphysis and mid-diaphysis of the tibia were analyzed histomorphometrically. Plasma osteocalcin, IGF-I, and urinary deoxypyridinoline were quantified. After 14 days of protein restriction, significant drops in plasma osteocalcin (13%) and IGF-I (37%), in periosteal formation (83%) and mineral apposition (49%) rates are observed, indicating a decreased osteoblast recruitment and activity. In cancellous bone, a significant decrease in active eroded surfaces (27%) and osteoclast number (24%) indicates a transient depression of resorption. In rats fed the 15% casein diet, rhIGF-I/IGFBP-3 increases cancellous (42%) and periosteal (600%) formation rates, indicating an increased osteoblast recruitment. In protein-restricted rats, rhIGF-I/IGFBP-3 fails to increase cancellous or periosteal bone formation and plasma osteocalcin is significantly lower than in 15% casein+rhIGF-I/ IGFBP-3 rats. Protein restriction induces osteoblast resistance to rhIGF-I/IGFBP-3 in both bone envelopes. Low plasma IGF-I and osteoblast resistance to IGF-I, may contribute to the impaired periosteal formation.

Animals↗

PubMed2000

Positive and negative control of the expression of parathyroid hormone (PTH)/PTH-related protein receptor via proximal promoter P3 in human osteoblast-like cells.

Three promoters, P1, P2, and P3, regulate the expression of the receptor for the human PTH/PTH -related protein. The P3 promoter, proximal to the gene, seems to be turned on in many tissues and to be the most active of the three in the human adult kidney. P3 is also active in human osteoblastic SaOS-2 cells. Its structure to function relationship is, however, still poorly understood. To address this issue we assayed, in transiently transfected SaOS-2 cells, the expression of reporter gene constructs containing truncated P3 promoter fragments and substitution mutants. We thus localized cis-acting elements essential for P3 promoter activity and identified two key Sp1 binding sites. We also found in the 5'-untranslated exon U4, transcribed from promoter P3, an element that inhibits the expression of the receptor and is not promoter specific. This study provides new insights into PTH receptor expression in human osteoblast-like cells.

5' Untranslated Regions↗