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Clinical exome sequencing (CES) is an established method for genetic diagnosis that is commonly used in clinical practices. Studies examining the CES experience for families have primarily been non-Latino white participants who speak English. To begin to address how these experiences may differ in other populations, we conducted in-depth semi-structured interviews. Interviews were completed with 22 Latino parents (14 in English; 8 in Spanish) of children who had pediatric CES at Columbia University Medical Center and received results within three to 20 months of the interview. We also measured acculturation with a standardized scale. Similar to prior studies, parents reported varied emotional reactions to their child’s results. Parents largely understood their child’s CES results though were not always able to correctly recall recurrence risk. The majority of participants reported feelings of anxiety while waiting for CES results. Some parents, particularly those not fluent in English with lower acculturation scores, reported language barriers to their understanding of the testing and their child’s care. Faith appeared to be a positive coping mechanism that was more frequently reported by participants with lower acculturation scores. Our findings are consistent with many of the previous studies of parental experience of CES but highlight some key findings that warrant further study and potentially inform practice. Larger studies should explore potential associations between acculturation and parental understanding or emotional response to results. The minimal language barriers reported by Spanish-speaking patients reiterates the importance of a Spanish-speaking provider, when possible, and bilingual resources.

Clinical exome sequencing (CES) is an established method for genetic diagnosis that is commonly used in clinical practices. Studies examining the CES experience for families have primarily been non-Latino white participants who speak English. To begin to address how these experiences may differ in other populations, we conducted in-depth semi-structured interviews. Interviews were completed with 22 Latino parents (14 in English; 8 in Spanish) of children who had pediatric CES at Columbia University Medical Center and received results within three to 20 months of the interview. We also measured acculturation with a standardized scale. Similar to prior studies, parents reported varied emotional reactions to their child’s results. Parents largely understood their child’s CES results though were not always able to correctly recall recurrence risk. The majority of participants reported feelings of anxiety while waiting for CES results. Some parents, particularly those not fluent in English with lower acculturation scores, reported language barriers to their understanding of the testing and their child’s care. Faith appeared to be a positive coping mechanism that was more frequently reported by participants with lower acculturation scores. Our findings are consistent with many of the previous studies of parental experience of CES but highlight some key findings that warrant further study and potentially inform practice. Larger studies should explore potential associations between acculturation and parental understanding or emotional response to results. The minimal language barriers reported by Spanish-speaking patients reiterates the importance of a Spanish-speaking provider, when possible, and bilingual resources.

Clinical exome sequencing (CES) is an established method for genetic diagnosis that is commonly used in clinical practices. Studies examining the CES experience for families have primarily been non-Latino white participants who speak English. To begin to address how these experiences may differ in other populations, we conducted in-depth semi-structured interviews. Interviews were completed with 22 Latino parents (14 in English; 8 in Spanish) of children who had pediatric CES at Columbia University Medical Center and received results within three to 20 months of the interview. We also measured acculturation with a standardized scale. Similar to prior studies, parents reported varied emotional reactions to their child’s results. Parents largely understood their child’s CES results though were not always able to correctly recall recurrence risk. The majority of participants reported feelings of anxiety while waiting for CES results. Some parents, particularly those not fluent in English with lower acculturation scores, reported language barriers to their understanding of the testing and their child’s care. Faith appeared to be a positive coping mechanism that was more frequently reported by participants with lower acculturation scores. Our findings are consistent with many of the previous studies of parental experience of CES but highlight some key findings that warrant further study and potentially inform practice. Larger studies should explore potential associations between acculturation and parental understanding or emotional response to results. The minimal language barriers reported by Spanish-speaking patients reiterates the importance of a Spanish-speaking provider, when possible, and bilingual resources.

Clinical exome sequencing (CES) is an established method for genetic diagnosis that is commonly used in clinical practices. Studies examining the CES experience for families have primarily been non-Latino white participants who speak English. To begin to address how these experiences may differ in other populations, we conducted in-depth semi-structured interviews. Interviews were completed with 22 Latino parents (14 in English; 8 in Spanish) of children who had pediatric CES at Columbia University Medical Center and received results within three to 20 months of the interview. We also measured acculturation with a standardized scale. Similar to prior studies, parents reported varied emotional reactions to their child’s results. Parents largely understood their child’s CES results though were not always able to correctly recall recurrence risk. The majority of participants reported feelings of anxiety while waiting for CES results. Some parents, particularly those not fluent in English with lower acculturation scores, reported language barriers to their understanding of the testing and their child’s care. Faith appeared to be a positive coping mechanism that was more frequently reported by participants with lower acculturation scores. Our findings are consistent with many of the previous studies of parental experience of CES but highlight some key findings that warrant further study and potentially inform practice. Larger studies should explore potential associations between acculturation and parental understanding or emotional response to results. The minimal language barriers reported by Spanish-speaking patients reiterates the importance of a Spanish-speaking provider, when possible, and bilingual resources.

Clinical exome sequencing (CES) is an established method for genetic diagnosis that is commonly used in clinical practices. Studies examining the CES experience for families have primarily been non-Latino white participants who speak English. To begin to address how these experiences may differ in other populations, we conducted in-depth semi-structured interviews. Interviews were completed with 22 Latino parents (14 in English; 8 in Spanish) of children who had pediatric CES at Columbia University Medical Center and received results within three to 20 months of the interview. We also measured acculturation with a standardized scale. Similar to prior studies, parents reported varied emotional reactions to their child’s results. Parents largely understood their child’s CES results though were not always able to correctly recall recurrence risk. The majority of participants reported feelings of anxiety while waiting for CES results. Some parents, particularly those not fluent in English with lower acculturation scores, reported language barriers to their understanding of the testing and their child’s care. Faith appeared to be a positive coping mechanism that was more frequently reported by participants with lower acculturation scores. Our findings are consistent with many of the previous studies of parental experience of CES but highlight some key findings that warrant further study and potentially inform practice. Larger studies should explore potential associations between acculturation and parental understanding or emotional response to results. The minimal language barriers reported by Spanish-speaking patients reiterates the importance of a Spanish-speaking provider, when possible, and bilingual resources.

Clinical exome sequencing (CES) is an established method for genetic diagnosis that is commonly used in clinical practices. Studies examining the CES experience for families have primarily been non-Latino white participants who speak English. To begin to address how these experiences may differ in other populations, we conducted in-depth semi-structured interviews. Interviews were completed with 22 Latino parents (14 in English; 8 in Spanish) of children who had pediatric CES at Columbia University Medical Center and received results within three to 20 months of the interview. We also measured acculturation with a standardized scale. Similar to prior studies, parents reported varied emotional reactions to their child’s results. Parents largely understood their child’s CES results though were not always able to correctly recall recurrence risk. The majority of participants reported feelings of anxiety while waiting for CES results. Some parents, particularly those not fluent in English with lower acculturation scores, reported language barriers to their understanding of the testing and their child’s care. Faith appeared to be a positive coping mechanism that was more frequently reported by participants with lower acculturation scores. Our findings are consistent with many of the previous studies of parental experience of CES but highlight some key findings that warrant further study and potentially inform practice. Larger studies should explore potential associations between acculturation and parental understanding or emotional response to results. The minimal language barriers reported by Spanish-speaking patients reiterates the importance of a Spanish-speaking provider, when possible, and bilingual resources.

Clinical exome sequencing (CES) is an established method for genetic diagnosis that is commonly used in clinical practices. Studies examining the CES experience for families have primarily been non-Latino white participants who speak English. To begin to address how these experiences may differ in other populations, we conducted in-depth semi-structured interviews. Interviews were completed with 22 Latino parents (14 in English; 8 in Spanish) of children who had pediatric CES at Columbia University Medical Center and received results within three to 20 months of the interview. We also measured acculturation with a standardized scale. Similar to prior studies, parents reported varied emotional reactions to their child’s results. Parents largely understood their child’s CES results though were not always able to correctly recall recurrence risk. The majority of participants reported feelings of anxiety while waiting for CES results. Some parents, particularly those not fluent in English with lower acculturation scores, reported language barriers to their understanding of the testing and their child’s care. Faith appeared to be a positive coping mechanism that was more frequently reported by participants with lower acculturation scores. Our findings are consistent with many of the previous studies of parental experience of CES but highlight some key findings that warrant further study and potentially inform practice. Larger studies should explore potential associations between acculturation and parental understanding or emotional response to results. The minimal language barriers reported by Spanish-speaking patients reiterates the importance of a Spanish-speaking provider, when possible, and bilingual resources.

Clinical exome sequencing (CES) is an established method for genetic diagnosis that is commonly used in clinical practices. Studies examining the CES experience for families have primarily been non-Latino white participants who speak English. To begin to address how these experiences may differ in other populations, we conducted in-depth semi-structured interviews. Interviews were completed with 22 Latino parents (14 in English; 8 in Spanish) of children who had pediatric CES at Columbia University Medical Center and received results within three to 20 months of the interview. We also measured acculturation with a standardized scale. Similar to prior studies, parents reported varied emotional reactions to their child’s results. Parents largely understood their child’s CES results though were not always able to correctly recall recurrence risk. The majority of participants reported feelings of anxiety while waiting for CES results. Some parents, particularly those not fluent in English with lower acculturation scores, reported language barriers to their understanding of the testing and their child’s care. Faith appeared to be a positive coping mechanism that was more frequently reported by participants with lower acculturation scores. Our findings are consistent with many of the previous studies of parental experience of CES but highlight some key findings that warrant further study and potentially inform practice. Larger studies should explore potential associations between acculturation and parental understanding or emotional response to results. The minimal language barriers reported by Spanish-speaking patients reiterates the importance of a Spanish-speaking provider, when possible, and bilingual resources.

Clinical exome sequencing (CES) is an established method for genetic diagnosis that is commonly used in clinical practices. Studies examining the CES experience for families have primarily been non-Latino white participants who speak English. To begin to address how these experiences may differ in other populations, we conducted in-depth semi-structured interviews. Interviews were completed with 22 Latino parents (14 in English; 8 in Spanish) of children who had pediatric CES at Columbia University Medical Center and received results within three to 20 months of the interview. We also measured acculturation with a standardized scale. Similar to prior studies, parents reported varied emotional reactions to their child’s results. Parents largely understood their child’s CES results though were not always able to correctly recall recurrence risk. The majority of participants reported feelings of anxiety while waiting for CES results. Some parents, particularly those not fluent in English with lower acculturation scores, reported language barriers to their understanding of the testing and their child’s care. Faith appeared to be a positive coping mechanism that was more frequently reported by participants with lower acculturation scores. Our findings are consistent with many of the previous studies of parental experience of CES but highlight some key findings that warrant further study and potentially inform practice. Larger studies should explore potential associations between acculturation and parental understanding or emotional response to results. The minimal language barriers reported by Spanish-speaking patients reiterates the importance of a Spanish-speaking provider, when possible, and bilingual resources.

Reducing population salt intake is a global public health priority due to the potential to save lives and reduce the burden on the healthcare system through decreased blood pressure. This implementation science research project set out to measure salt consumption patterns and to assess the impact of a complex, multi-faceted intervention to reduce population salt intake in Fiji between 2012 and 2016. The intervention combined initiatives to engage food businesses to reduce salt in foods and meals with targeted consumer behavior change programs. There were 169 participants at baseline (response rate 28.2%) and 272 at 20 months (response rate 22.4%). The mean salt intake from 24-h urine samples was estimated to be 11.7 grams per day (g/d) at baseline and 10.3 g/d after 20 months (difference: −1.4 g/day, 95% CI −3.1 to 0.3, p = 0.115). Sub-analysis showed a statistically significant reduction in female salt intake in the Central Division but no differential impact in relation to age or ethnicity. Whilst the low response rate means it is not possible to draw firm conclusions about these changes, the population salt intake in Fiji, at 10.3 g/day, is still twice the World Health Organization’s (WHO) recommended maximum intake. This project also assessed iodine intake levels in women of child-bearing age and found that they were within recommended guidelines. Existing policies and programs to reduce salt intake and prevent iodine deficiency need to be maintained or strengthened. Monitoring to assess changes in salt intake and to ensure that iodine levels remain adequate should be built into future surveys.

Background: The imperative to improve global health has prompted transnational research partnerships to investigate common health issues on a larger scale. The Global Alliance for Chronic Diseases (GACD) is an alliance of national research funding agencies. To enhance research funded by GACD members, this study aimed to standardise data collection methods across the 15 GACD hypertension research teams and evaluate the uptake of these standardised measurements. Furthermore we describe concerns and difficulties associated with the data harmonisation process highlighted and debated during annual meetings of the GACD funded investigators. With these concerns and issues in mind, a working group comprising representatives from the 15 studies iteratively identified and proposed a set of common measures for inclusion in each of the teams' data collection plans. One year later all teams were asked which consensus measures had been implemented. Result(s): Important issues were identified during the data harmonisation process relating to data ownership, sharing methodologies and ethical concerns. Measures were assessed across eight domains; demographic; dietary; clinical and anthropometric; medical history; hypertension knowledge; physical activity; behavioural (smoking and alcohol); and biochemical domains. Identifying validated measures relevant across a variety of settings presented some difficulties. The resulting GACD hypertension data dictionary comprises 67 consensus measures. Of the 14 responding teams, only two teams were including more than 50 consensus variables, five teams were including between 25 and 50 consensus variables and four teams were including between 6 and 24 consensus variables, one team did not provide details of the variables collected and two teams did not include any of the consensus variables as the project had already commenced or the measures were not relevant to their study. Conclusion(s): Deriving consensus measures across diverse research pro

Background: The imperative to improve global health has prompted transnational research partnerships to investigate common health issues on a larger scale. The Global Alliance for Chronic Diseases (GACD) is an alliance of national research funding agencies. To enhance research funded by GACD members, this study aimed to standardise data collection methods across the 15 GACD hypertension research teams and evaluate the uptake of these standardised measurements. Furthermore we describe concerns and difficulties associated with the data harmonisation process highlighted and debated during annual meetings of the GACD funded investigators. With these concerns and issues in mind, a working group comprising representatives from the 15 studies iteratively identified and proposed a set of common measures for inclusion in each of the teams' data collection plans. One year later all teams were asked which consensus measures had been implemented. Result(s): Important issues were identified during the data harmonisation process relating to data ownership, sharing methodologies and ethical concerns. Measures were assessed across eight domains; demographic; dietary; clinical and anthropometric; medical history; hypertension knowledge; physical activity; behavioural (smoking and alcohol); and biochemical domains. Identifying validated measures relevant across a variety of settings presented some difficulties. The resulting GACD hypertension data dictionary comprises 67 consensus measures. Of the 14 responding teams, only two teams were including more than 50 consensus variables, five teams were including between 25 and 50 consensus variables and four teams were including between 6 and 24 consensus variables, one team did not provide details of the variables collected and two teams did not include any of the consensus variables as the project had already commenced or the measures were not relevant to their study. Conclusion(s): Deriving consensus measures across diverse research pro

Reducing population salt intake is a global public health priority due to the potential to save lives and reduce the burden on the healthcare system through decreased blood pressure. This implementation science research project set out to measure salt consumption patterns and to assess the impact of a complex, multi-faceted intervention to reduce population salt intake in Fiji between 2012 and 2016. The intervention combined initiatives to engage food businesses to reduce salt in foods and meals with targeted consumer behavior change programs. There were 169 participants at baseline (response rate 28.2%) and 272 at 20 months (response rate 22.4%). The mean salt intake from 24-h urine samples was estimated to be 11.7 grams per day (g/d) at baseline and 10.3 g/d after 20 months (difference: -1.4 g/day, 95% CI -3.1 to 0.3, p = 0.115). Sub-analysis showed a statistically significant reduction in female salt intake in the Central Division but no differential impact in relation to age or ethnicity. Whilst the low response rate means it is not possible to draw firm conclusions about these changes, the population salt intake in Fiji, at 10.3 g/day, is still twice the World Health Organization's (WHO) recommended maximum intake. This project also assessed iodine intake levels in women of child-bearing age and found that they were within recommended guidelines. Existing policies and programs to reduce salt intake and prevent iodine deficiency need to be maintained or strengthened. Monitoring to assess changes in salt intake and to ensure that iodine levels remain adequate should be built into future surveys.

Reducing population salt intake is a global public health priority due to the potential to save lives and reduce the burden on the healthcare system through decreased blood pressure. This implementation science research project set out to measure salt consumption patterns and to assess the impact of a complex, multi-faceted intervention to reduce population salt intake in Fiji between 2012 and 2016. The intervention combined initiatives to engage food businesses to reduce salt in foods and meals with targeted consumer behavior change programs. There were 169 participants at baseline (response rate 28.2%) and 272 at 20 months (response rate 22.4%). The mean salt intake from 24-h urine samples was estimated to be 11.7 grams per day (g/d) at baseline and 10.3 g/d after 20 months (difference: -1.4 g/day, 95% CI -3.1 to 0.3, p = 0.115). Sub-analysis showed a statistically significant reduction in female salt intake in the Central Division but no differential impact in relation to age or ethnicity. Whilst the low response rate means it is not possible to draw firm conclusions about these changes, the population salt intake in Fiji, at 10.3 g/day, is still twice the World Health Organization's (WHO) recommended maximum intake. This project also assessed iodine intake levels in women of child-bearing age and found that they were within recommended guidelines. Existing policies and programs to reduce salt intake and prevent iodine deficiency need to be maintained or strengthened. Monitoring to assess changes in salt intake and to ensure that iodine levels remain adequate should be built into future surveys.

Reducing population salt intake is a global public health priority due to the potential to save lives and reduce the burden on the healthcare system through decreased blood pressure. This implementation science research project set out to measure salt consumption patterns and to assess the impact of a complex, multi-faceted intervention to reduce population salt intake in Fiji between 2012 and 2016. The intervention combined initiatives to engage food businesses to reduce salt in foods and meals with targeted consumer behavior change programs. There were 169 participants at baseline (response rate 28.2%) and 272 at 20 months (response rate 22.4%). The mean salt intake from 24-h urine samples was estimated to be 11.7 grams per day (g/d) at baseline and 10.3 g/d after 20 months (difference: -1.4 g/day, 95% CI -3.1 to 0.3, p = 0.115). Sub-analysis showed a statistically significant reduction in female salt intake in the Central Division but no differential impact in relation to age or ethnicity. Whilst the low response rate means it is not possible to draw firm conclusions about these changes, the population salt intake in Fiji, at 10.3 g/day, is still twice the World Health Organization's (WHO) recommended maximum intake. This project also assessed iodine intake levels in women of child-bearing age and found that they were within recommended guidelines. Existing policies and programs to reduce salt intake and prevent iodine deficiency need to be maintained or strengthened. Monitoring to assess changes in salt intake and to ensure that iodine levels remain adequate should be built into future surveys.

Osteoporosis is a common problem of aging and results from a failure of homeostatic mechanisms to regulate osteogenesis and mineralization. Bovine and human forms of fetuin glycoprotein bind to the transforming growth factor (TGF)-beta/BMP (bone morphogenic protein) cytokines and block their osteogenic activity in cell culture assays (Demetriou, M., Binkert, C., Sukhu, B., Tenenbaum, H. C., and Dennis, J. W. (1996) J. Biol. Chem. 271, 12755-12761). Fetuin is a prominent serum glycoprotein and a major noncollagenous component of mineralized bone in mammals. In this study, we show that recombinant fetuin and native serum protein have similar potency as inhibitors of osteogenesis in dexamethasone-treated rat bone marrow cell cultures (dex-RBMC). Recombinant bovine fetuin also bound to TGF-beta1 and BMP-2 in vitro with kinetics similar to native fetuin. Although TGF-beta1 is required for osteogenesis in dex-RBMC, the cytokine also inhibited osteogenesis at concentrations >/=10 pM. Titration of fetuin or anti-TGF-beta1 antibodies into the bone marrow cultures in the presence of 10 pM TGF-beta1 restored osteogenesis, whereas titrations of the same reagents into cultures with 0.3 pM added TGF-beta1 were inhibitory, confirming the biphasic nature of the TGF-beta1 response. Suppression of osteogenesis by both TGF-beta1 and the antagonist proteins required their presence within the first 6 days of culture, well before mineralization at 10-12 days. Northern analysis showed that both fetuin and high dose TGF-beta1 suppressed expression of the bone-associated transcripts alkaline phosphatase, osteopontin, collagen type I, and bone sialoprotein. The suppression of osteogenesis by fetuin and by high dose TGF-beta1 was accompanied by the differentiation of an alternate cell lineage with adipocyte characteristics. In summary, the biphasic osteogenic response to TGF-beta1 suggests that overlapping gradients of TGF-beta/BMP cytokines and fetuin regulate osteogenesis in remodeling b

Osteoporosis is a common problem of aging and results from a failure of homeostatic mechanisms to regulate osteogenesis and mineralization. Bovine and human forms of fetuin glycoprotein bind to the transforming growth factor (TGF)-beta/BMP (bone morphogenic protein) cytokines and block their osteogenic activity in cell culture assays (Demetriou, M., Binkert, C., Sukhu, B., Tenenbaum, H. C., and Dennis, J. W. (1996) J. Biol. Chem. 271, 12755-12761). Fetuin is a prominent serum glycoprotein and a major noncollagenous component of mineralized bone in mammals. In this study, we show that recombinant fetuin and native serum protein have similar potency as inhibitors of osteogenesis in dexamethasone-treated rat bone marrow cell cultures (dex-RBMC). Recombinant bovine fetuin also bound to TGF-beta1 and BMP-2 in vitro with kinetics similar to native fetuin. Although TGF-beta1 is required for osteogenesis in dex-RBMC, the cytokine also inhibited osteogenesis at concentrations >/=10 pM. Titration of fetuin or anti-TGF-beta1 antibodies into the bone marrow cultures in the presence of 10 pM TGF-beta1 restored osteogenesis, whereas titrations of the same reagents into cultures with 0.3 pM added TGF-beta1 were inhibitory, confirming the biphasic nature of the TGF-beta1 response. Suppression of osteogenesis by both TGF-beta1 and the antagonist proteins required their presence within the first 6 days of culture, well before mineralization at 10-12 days. Northern analysis showed that both fetuin and high dose TGF-beta1 suppressed expression of the bone-associated transcripts alkaline phosphatase, osteopontin, collagen type I, and bone sialoprotein. The suppression of osteogenesis by fetuin and by high dose TGF-beta1 was accompanied by the differentiation of an alternate cell lineage with adipocyte characteristics. In summary, the biphasic osteogenic response to TGF-beta1 suggests that overlapping gradients of TGF-beta/BMP cytokines and fetuin regulate osteogenesis in remodeling b

The serum glycoprotein fetuin is expressed during embryogenesis in multiple tissues including limb buds and has been shown to promote bone remodeling and stimulate cell proliferation in vitro. In this report, we demonstrate that fetuin antagonizes the antiproliferative action of transforming growth factor-beta1 (TGF-beta1) in cell cultures. Surface plasmon resonance measurements show that fetuin binds directly to TGF-beta1 and TGF-beta2 and with greater affinity to the TGF-beta-related bone morphogenetic proteins (BMP-2, BMP-4, and BMP-6). In a competitive enzyme-linked immunosorbent assay, fetuin blocked binding of TGF-beta1 to the extracellular domain of TGF-beta receptor type II (TbetaRII), one of the primary TGF-beta-binding receptors. A comparison of fetuin and TbetaRII shows homology in an 18-19-amino acid sequence, which we have designated TGF-beta receptor II homology 1 domain (TRH1). Since the TRH1 sequence is known to form a disulfide loop in fetuin, cyclized TRH1 peptides from both fetuin and TbetaRII were chemically synthesized and tested for cytokine binding activity. Cyclized TRH1 peptide from TbetaRII bound to TGF-beta1 with greater affinity than to BMP-2, while the cyclized TRH1 peptide from fetuin bound preferentially to BMP-2. Finally, fetuin or neutralizing anti-TGF-beta antibodies blocked osteogenesis and deposition of calcium-containing matrix in cultures of dexamethasone-treated rat bone marrow cells. In summary, these experiments define the TRH1 peptide loop as a cytokine-binding domain in both TbetaRII and fetuin and suggest that fetuin is a natural antagonist of TGF-beta and BMP activities.

The serum glycoprotein fetuin is expressed during embryogenesis in multiple tissues including limb buds and has been shown to promote bone remodeling and stimulate cell proliferation in vitro. In this report, we demonstrate that fetuin antagonizes the antiproliferative action of transforming growth factor-beta1 (TGF-beta1) in cell cultures. Surface plasmon resonance measurements show that fetuin binds directly to TGF-beta1 and TGF-beta2 and with greater affinity to the TGF-beta-related bone morphogenetic proteins (BMP-2, BMP-4, and BMP-6). In a competitive enzyme-linked immunosorbent assay, fetuin blocked binding of TGF-beta1 to the extracellular domain of TGF-beta receptor type II (TbetaRII), one of the primary TGF-beta-binding receptors. A comparison of fetuin and TbetaRII shows homology in an 18-19-amino acid sequence, which we have designated TGF-beta receptor II homology 1 domain (TRH1). Since the TRH1 sequence is known to form a disulfide loop in fetuin, cyclized TRH1 peptides from both fetuin and TbetaRII were chemically synthesized and tested for cytokine binding activity. Cyclized TRH1 peptide from TbetaRII bound to TGF-beta1 with greater affinity than to BMP-2, while the cyclized TRH1 peptide from fetuin bound preferentially to BMP-2. Finally, fetuin or neutralizing anti-TGF-beta antibodies blocked osteogenesis and deposition of calcium-containing matrix in cultures of dexamethasone-treated rat bone marrow cells. In summary, these experiments define the TRH1 peptide loop as a cytokine-binding domain in both TbetaRII and fetuin and suggest that fetuin is a natural antagonist of TGF-beta and BMP activities.