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Serum Dikkopf-1 levels in postmenopausal women with established osteoporosis before and after treatment with teriparatide
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Abstracts / Bone 44 (2009) S253–S338
non-overlapping Msx1 and Msx2 expression patterns suggested that these two homeogenes would play non redundant roles in skeletal growth, targeting basal bone for Msx1 and alveolar bone related to teeth for Msx2, respectively. These data provide some clues in human genetics related to Msx homeogenes: i.e. a detailed analysis of the late phenotype relied to Msx2 mutation and the identification of distinct regional impact of these homeogenes during post-natal growth in the oral skeleton. Conflict of interest: None declared. doi:10.1016/j.bone.2009.03.532
P107 Serum Dikkopf-1 levels in postmenopausal women with established osteoporosis before and after treatment with teriparatide A.D. Anastasilakisa,*, S.A. Polyzosb, A. Avramidisc, K. Toulisa, A. Giomisid, A. Papatheodoroue, E. Terpose a Endocrinology, 424 Military Hospital b Second Medical Clinic, Aristotle University c Endocrinology, Hippokration General Hospital d Gynaecology, 424 Military Hospital, Thessaloniki e Medical Research, 251 General Air Force Hospital, Athens, Greece Background/aims. The mechanisms regulating the anabolic response of the skeleton to intermittent exogenous parathyroid hormone are not fully elucidated. The aim of this prospective cohort study was to evaluate serum levels of Dikkopf-1 (Dkk-1) in postmenopausal women with established osteoporosis and their changes with teriparatide (TPTD – human recombinant PTH 1–34). Methods. Thirty-one postmenopausal Caucasian women with established osteoporosis (mean age 66.3 ± 1.4 years) received daily injections of 20 μg TPTD for 18 months. Follow-up was continued for another six months after treatment discontinuation (totally 24 months). Serum samples for total calcium (Ca), intact PTH (iPTH), bone-specific alkaline phosphatase (BSAP) and Dkk-1 were obtained at baseline, six months, 18 months and 24 months after TPTD initiation. Lumbar spine bone mineral density (BMD) was measured before and after 18 months of TPTD treatment. Sixteen age- and gender-matched healthy controls were also analyzed at baseline. Results. Serum Dkk-1 levels at baseline were significantly higher in osteoporotic women compared with controls (p < 0.002). Dkk-1 increased significantly during TPTD administration (p < 0.044) and decreased to baseline six months after TPTD discontinuation. Dkk-1 change was positively correlated to Ca (r = 0.530, p = 0.004) and negatively correlated to iPTH change (r = -0.398, p = 0.040). There was no correlation between Dkk-1 and BMD changes. Conclusion. Our data suggest that Dkk-1 levels are increased in women with postmenopausal osteoporosis. TPTD therapy results in further increase of Dkk-1 that may be compensative to the TPTDinduced enhanced Wnt-signaling. Increased Dkk-1 may be required for the late-stage osteoblast differentiation, bone matrix mineralization and the increased osteoclastogenesis that characterizes TPTD. Conflict of interest: None declared. doi:10.1016/j.bone.2009.03.533
P108 Involvement of the car in smooth muscle cell mineralization during atherosclerosis A. Caudrillier⁎, L. Petit, C. Boudot, Z. Massy, M. Brazier, R. Mentaverri, S. Kamel Faculté de Pharmacie, UPJV, INSERM ERI-12, Amiens, France
Background/aims: Vascular calcification is associated with an increased risk of myocardial infarction. Recent evidence suggests that extracellular calcium (Ca2+o) and vascular smooth muscle cells (SMC) play a pivotal role in the pathogenesis of vascular calcification. Trans-differentiation of human SMC into calcified vascular cells (CVC) in the intima of arteries is a pre-requisite for plaque calcification in atherosclerosis. Methods/Results: In the present study, we found that Ca2+oinduces SMC trans-differentiation and mineralization in a concentration-dependent manner through the activation of the calcium sensing receptor (CaR). This phenomenon occurs in a rapid manner, and under our culture conditions the first mineralized nodules appear after 5 days. SMC transfection with SiRNA directed against the CaR increases both the size of mineralized plaques and accelerates the speed of their development, under our culture conditions only 3 days were necessary to obtain the first mineralized structures. Confirming the role play by the CaR in this phenomenon, addition of the calcimimetic NPS-R568 (3.10–7 M) to the in vitro culture strongly inhibited the effects exerted by calcium. It is of note, however, that SMC transfected with CaR-SiRNA lose their capacity to respond to calcimimetics and, more surprisingly, appear more prone to respond to calcium, suggesting that the CaR expressed by the SMC is protective against calcium-induced vascular calcification. Apparition of mineralization was shown to be linked to loss of alpha-actin in SMC, indicative of trans-differentiation of SMC into CVC in response to calcium treatment. Similarly, the loss of alpha-actin appeared to be amplified in cells transfected with the CaR-SiRNA. Conclusion: In conclusion, this study gives novel insight into the role played by calcium, through the activation of the CaR, in SMC trans-differentiation and/or mineralization, and suggests that this G protein coupled receptor is protective against the development of vascular calcification. Taken together, these data also suggest that the CaR is a key actor in the installation and development of atherosclerotic lesions.Funding: Projet structurant Region Picardie. Conflict of interest: None declared. doi:10.1016/j.bone.2009.03.534
P109 Localization of heparanase during palatal bone formation in palatogenesis in mice A. Hirataa,*, T. Tsujib, T. Uenoc, T. Yamadac, H. Imurad, T. Kagawac, T. Matsumurac, N. Moritanic, K. Mishimac, T. Sugaharad, H. Nakamurae a Oral Morphology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama, Japan b Graduate School of Natural and technology, Okayama University, Okayama c Oral and maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama d Division of Research and Treatment for Oral and Maxillofacial Congenital Anomalies, Aichigakuin University, Nagoya e Oral Histology, Matsumoto Dental University, Shiojiri, Japan Background/aims: Development of the mammalian secondary plate is regulated by multiple steps, and the palatal bone is observed after palate fusion. Several heparan sulfate proteoglycans (HSPGs) have been implicated in the regulation of ossification, bone remodeling and fracture healing, as several growth factors bind via heparan sulfate (HS) chains. In additionally, heparanase, an endoglucuronidase, was identified as a key enzyme responsible for cleavage of the HS chain in HSPGs. Here, we determined the immunolocalization pattern of heparanase in order to clarify its role in murine palatal bone formation in palatogenesis.
Abstracts / Bone 44 (2009) S253–S338
non-overlapping Msx1 and Msx2 expression patterns suggested that these two homeogenes would play non redundant roles in skeletal growth, targeting basal bone for Msx1 and alveolar bone related to teeth for Msx2, respectively. These data provide some clues in human genetics related to Msx homeogenes: i.e. a detailed analysis of the late phenotype relied to Msx2 mutation and the identification of distinct regional impact of these homeogenes during post-natal growth in the oral skeleton. Conflict of interest: None declared. doi:10.1016/j.bone.2009.03.532
P107 Serum Dikkopf-1 levels in postmenopausal women with established osteoporosis before and after treatment with teriparatide A.D. Anastasilakisa,*, S.A. Polyzosb, A. Avramidisc, K. Toulisa, A. Giomisid, A. Papatheodoroue, E. Terpose a Endocrinology, 424 Military Hospital b Second Medical Clinic, Aristotle University c Endocrinology, Hippokration General Hospital d Gynaecology, 424 Military Hospital, Thessaloniki e Medical Research, 251 General Air Force Hospital, Athens, Greece Background/aims. The mechanisms regulating the anabolic response of the skeleton to intermittent exogenous parathyroid hormone are not fully elucidated. The aim of this prospective cohort study was to evaluate serum levels of Dikkopf-1 (Dkk-1) in postmenopausal women with established osteoporosis and their changes with teriparatide (TPTD – human recombinant PTH 1–34). Methods. Thirty-one postmenopausal Caucasian women with established osteoporosis (mean age 66.3 ± 1.4 years) received daily injections of 20 μg TPTD for 18 months. Follow-up was continued for another six months after treatment discontinuation (totally 24 months). Serum samples for total calcium (Ca), intact PTH (iPTH), bone-specific alkaline phosphatase (BSAP) and Dkk-1 were obtained at baseline, six months, 18 months and 24 months after TPTD initiation. Lumbar spine bone mineral density (BMD) was measured before and after 18 months of TPTD treatment. Sixteen age- and gender-matched healthy controls were also analyzed at baseline. Results. Serum Dkk-1 levels at baseline were significantly higher in osteoporotic women compared with controls (p < 0.002). Dkk-1 increased significantly during TPTD administration (p < 0.044) and decreased to baseline six months after TPTD discontinuation. Dkk-1 change was positively correlated to Ca (r = 0.530, p = 0.004) and negatively correlated to iPTH change (r = -0.398, p = 0.040). There was no correlation between Dkk-1 and BMD changes. Conclusion. Our data suggest that Dkk-1 levels are increased in women with postmenopausal osteoporosis. TPTD therapy results in further increase of Dkk-1 that may be compensative to the TPTDinduced enhanced Wnt-signaling. Increased Dkk-1 may be required for the late-stage osteoblast differentiation, bone matrix mineralization and the increased osteoclastogenesis that characterizes TPTD. Conflict of interest: None declared. doi:10.1016/j.bone.2009.03.533
P108 Involvement of the car in smooth muscle cell mineralization during atherosclerosis A. Caudrillier⁎, L. Petit, C. Boudot, Z. Massy, M. Brazier, R. Mentaverri, S. Kamel Faculté de Pharmacie, UPJV, INSERM ERI-12, Amiens, France
Background/aims: Vascular calcification is associated with an increased risk of myocardial infarction. Recent evidence suggests that extracellular calcium (Ca2+o) and vascular smooth muscle cells (SMC) play a pivotal role in the pathogenesis of vascular calcification. Trans-differentiation of human SMC into calcified vascular cells (CVC) in the intima of arteries is a pre-requisite for plaque calcification in atherosclerosis. Methods/Results: In the present study, we found that Ca2+oinduces SMC trans-differentiation and mineralization in a concentration-dependent manner through the activation of the calcium sensing receptor (CaR). This phenomenon occurs in a rapid manner, and under our culture conditions the first mineralized nodules appear after 5 days. SMC transfection with SiRNA directed against the CaR increases both the size of mineralized plaques and accelerates the speed of their development, under our culture conditions only 3 days were necessary to obtain the first mineralized structures. Confirming the role play by the CaR in this phenomenon, addition of the calcimimetic NPS-R568 (3.10–7 M) to the in vitro culture strongly inhibited the effects exerted by calcium. It is of note, however, that SMC transfected with CaR-SiRNA lose their capacity to respond to calcimimetics and, more surprisingly, appear more prone to respond to calcium, suggesting that the CaR expressed by the SMC is protective against calcium-induced vascular calcification. Apparition of mineralization was shown to be linked to loss of alpha-actin in SMC, indicative of trans-differentiation of SMC into CVC in response to calcium treatment. Similarly, the loss of alpha-actin appeared to be amplified in cells transfected with the CaR-SiRNA. Conclusion: In conclusion, this study gives novel insight into the role played by calcium, through the activation of the CaR, in SMC trans-differentiation and/or mineralization, and suggests that this G protein coupled receptor is protective against the development of vascular calcification. Taken together, these data also suggest that the CaR is a key actor in the installation and development of atherosclerotic lesions.Funding: Projet structurant Region Picardie. Conflict of interest: None declared. doi:10.1016/j.bone.2009.03.534
P109 Localization of heparanase during palatal bone formation in palatogenesis in mice A. Hirataa,*, T. Tsujib, T. Uenoc, T. Yamadac, H. Imurad, T. Kagawac, T. Matsumurac, N. Moritanic, K. Mishimac, T. Sugaharad, H. Nakamurae a Oral Morphology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama, Japan b Graduate School of Natural and technology, Okayama University, Okayama c Oral and maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama d Division of Research and Treatment for Oral and Maxillofacial Congenital Anomalies, Aichigakuin University, Nagoya e Oral Histology, Matsumoto Dental University, Shiojiri, Japan Background/aims: Development of the mammalian secondary plate is regulated by multiple steps, and the palatal bone is observed after palate fusion. Several heparan sulfate proteoglycans (HSPGs) have been implicated in the regulation of ossification, bone remodeling and fracture healing, as several growth factors bind via heparan sulfate (HS) chains. In additionally, heparanase, an endoglucuronidase, was identified as a key enzyme responsible for cleavage of the HS chain in HSPGs. Here, we determined the immunolocalization pattern of heparanase in order to clarify its role in murine palatal bone formation in palatogenesis.