Serum insulin-like growth factors and insulin-like growth factor-binding proteins: clinical implicationsC J Rosen
Maine Center for Osteoporosis Research and Education, St Joseph Hospital, 360 Broadway, Bangor, ME 04401, USA
Clin Chem 45:1384-90. 1999
..The IGFs remain a major area for basic and clinical investigations; future studies may define both diagnostic and therapeutic roles for these peptides or their related proteins in several disease states...
- A rational approach to evidence gaps in the management of osteoporosis
Clifford J Rosen
Maine Center for Osteoporosis Research and Education, St Joseph Hospital, Bangor, ME 04401, USA
Am J Med 118:1183-9. 2005
..Evidence gaps in each treatment scenario are presented, and rational approaches to management are suggested...
- The role of parathyroid hormone in the management of osteoporosis
Clifford J Rosen
The Maine Center for Osteoporosis Research and Education, St Joseph Hospital, Bangor, ME, USA
Horm Res 64:81-5. 2005
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- Congenic mice with low serum IGF-I have increased body fat, reduced bone mineral density, and an altered osteoblast differentiation program
Clifford J Rosen
The Jackson Laboratory, Bar Harbor, ME, USA
Bone 35:1046-58. 2004
..Congenic mice are useful models not only for mapping genes related to bone mass but also for elucidating the biology underlying various skeletal phenotypes associated with more subtle manipulation of the mouse genome...
- Insulin-like growth factor I and bone mineral density: experience from animal models and human observational studies
Clifford J Rosen
St Joseph Hospital, The Jackson Laboratory, 900 Broadway, Bldg No 2, Bangor, ME 04401, USA
Best Pract Res Clin Endocrinol Metab 18:423-35. 2004
..The implications from these animal models are far-reaching and suggest that newer approaches for manipulating the IGF regulatory system may one day be useful as therapeutic adjuncts for the treatment of osteoporosis...
- What's new with PTH in osteoporosis: where are we and where are we headed?
Clifford J Rosen
Maine Center for Osteoporosis Research and Education, St Joseph Hospital, 900 Broadway, Bldg 2, Bangor, ME 04401, USA
Trends Endocrinol Metab 15:229-33. 2004
..This review presents recent findings on PTH signaling in bone and discusses how they could be used to design randomized trials and establish clinical practice guidelines for this novel anabolic peptide...
- Vignettes in osteoporosis: a road map to successful therapeutics
Clifford J Rosen
Maine Center for Osteoporosis Research and Education, St Joseph Hospital, Bangor, Maine 04401, USA
J Bone Miner Res 19:3-10. 2004
..We describe five common clinical scenarios encountered in the practice of osteoporosis medicine and various road maps that could lead to successful therapy...
- Insulin-like growth factor I and calcium balance: evolving concepts of an evolutionary process
Clifford J Rosen
Jackson Laboratory and St. Joseph Hospital, Bangor, Maine 04401, USA
Endocrinology 144:4679-81. 2003
- The cellular and clinical parameters of anabolic therapy for osteoporosis
Clifford J Rosen
The Jackson Laboratory and St Joseph Hospital, Bangor, ME 04401, USA
Crit Rev Eukaryot Gene Expr 13:25-38. 2003
..Novel in vivo strategies, including temporal and conditional mutagenesis, will almost certainly lead to newer therapeutic paradigms for the treatment of postmenopausal osteoporosis...
- Mechanisms of disease: is osteoporosis the obesity of bone?
Clifford J Rosen
The Jackson Laboratory in Bar Harbor, ME 04401, USA
Nat Clin Pract Rheumatol 2:35-43. 2006
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- Clinical practice. Postmenopausal osteoporosis
Clifford J Rosen
St. Joseph Hospital, Maine Center for Osteoporosis Research and Education, Bangor, ME 04401, USA
N Engl J Med 353:595-603. 2005
- Growth hormone and aging
C J Rosen
The Maine Center for Osteoporosis Research and Education, St Joseph Hospital, Bangor 04401, USA
Endocrine 12:197-201. 2000
..Hence, there is less enthusiasm for reversing the changes of the "somatopause" with recombinant growth factors. An overview of these issues and the prospects for the future will be discussed in this article...
- Mapping quantitative trait loci for serum insulin-like growth factor-1 levels in mice
C J Rosen
Maine Center for Osteoporosis Research and Education, St Joseph Hospital, Bangor, ME 04401, USA
Bone 27:521-8. 2000
..C3H-6 congenic mice demonstrated effects on both the IGF-1 and BMD phenotypes. The genetic determinants of these Igf1sl QTLs will provide much insight into the regulation of IGF-1 and the subsequent acquisition of peak bone mass...
- Clinical review 123: Anabolic therapy for osteoporosis
C J Rosen
St Joseph Hospital, Bangor, Maine 04401, USA
J Clin Endocrinol Metab 86:957-64. 2001
..Fluoride, GH, insulin-like growth factor I, the statins, and PTH will be reviewed. Although still in development, approaches to combination therapy with antiresorptives and anabolic agents are also promising...
- Emerging anabolic treatments for osteoporosis
C J Rosen
Maine Center for Osteoporosis Research and Education, St Joseph Hospital, Bangor, USA
Rheum Dis Clin North Am 27:215-33, viii. 2001
..The two most promising agents, parathyroid hormone (PTH) and GH/IGF-I, act to increase osteoblast mediated bone formation. A review of the potential usefulness of PTH and GH/IGF-I is presented...
- Treatment of postmenopausal osteoporosis: an evidence-based approach
C J Rosen
Maine Center for Osteoporosis Research and Education, St Joseph Hospital, Bangor, ME, USA
Rev Endocr Metab Disord 2:35-43. 2001
..What is certain, is that there are now cost effective treatments for this disease. It remains up to the practicing physician to select, based on the existing evidence, treatments most appropriate for the individual patient...
- Marrow fat and the bone microenvironment: developmental, functional, and pathological implications
Clifford J Rosen
Maine Medical Center Research Institute, Scarborough, ME 04041, USA
Crit Rev Eukaryot Gene Expr 19:109-24. 2009
..However, more studies are needed to understand the interrelationship among hematopoietic, osteoblastic, and adipogenic cells within the marrow niche...
- Fat targets for skeletal health
Masanobu Kawai
Maine Medical Center Research Institute, Scarborough, ME 04074 7205, USA
Nat Rev Rheumatol 5:365-72. 2009
..Hence, a more complete picture of energy utilization and skeletal remodeling will be required to bring any potential agents into the future clinical armamentarium...
- Nocturnin: a circadian target of Pparg-induced adipogenesis
Masanobu Kawai
Maine Medical Center Research Institute, Scarborough, Maine, USA
Ann N Y Acad Sci 1192:131-8. 2010
..Defining the function of nocturnin in peripheral tissues should provide new insights into lineage allocation and the intimate relationship between nuclear receptors and physiologic timekeeping...
- PPARG by dietary fat interaction influences bone mass in mice and humans
Cheryl L Ackert-Bicknell
The Jackson Laboratory, Bar Harbor, Maine 04609, USA
J Bone Miner Res 23:1398-408. 2008
..These findings suggest that dietary fat has a significant influence on BMD that is dependent on the alleles present for the PPARG gene...
- PPARgamma2 nuclear receptor controls multiple regulatory pathways of osteoblast differentiation from marrow mesenchymal stem cells
Keith R Shockley
The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA
J Cell Biochem 106:232-46. 2009
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- Generation of a new congenic mouse strain to test the relationships among serum insulin-like growth factor I, bone mineral density, and skeletal morphology in vivo
Mary L Bouxsein
The The Jackson Laboratory, Bar Harbor, Maine, USA
J Bone Miner Res 17:570-9. 2002
..This locus also influences bone density and morphology, with more dramatic effects in cancellous bone than in cortical bone...
- Strain-specific effects of rosiglitazone on bone mass, body composition, and serum insulin-like growth factor-I
Cheryl L Ackert-Bicknell
The Jackson Laboratory, Bar Harbor, Maine 04609, USA
Endocrinology 150:1330-40. 2009
..The divergent skeletal responses to rosiglitazone in this study suggest the existence of a strong genetic background effect...
- Nocturnin suppresses igf1 expression in bone by targeting the 3' untranslated region of igf1 mRNA
Masanobu Kawai
Center for Translational Research, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, Maine 04074 7205, USA
Endocrinology 151:4861-70. 2010
..Posttranscriptional regulation of Igf1 may be critically important during skeletal acquisition and maintenance...
- Mouse models for understanding the growth hormone insulin-like growth factor-I axis
Clifford J Rosen
Maine Center for Osteoporosis Research and Education, St Joseph Hospital, Bangor, ME 04401, USA
Horm Res 68:2-4. 2007
..CONCLUSIONS: Mouse models continue to deepen our understanding of IGF-I signaling and the role of IGF-I in determining marrow stromal cell fate...
- Congenic strains of mice for verification and genetic decomposition of quantitative trait loci for femoral bone mineral density
Kathryn L Shultz
The Jackson Laboratory, Bar Harbor, Maine 04609, USA
J Bone Miner Res 18:175-85. 2003
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- Bone, fat, and body composition: evolving concepts in the pathogenesis of osteoporosis
Clifford J Rosen
Maine Medical Center Research Institute, Scarborough, ME 04074, USA
Am J Med 122:409-14. 2009
..This article explores these relationships in the context of a new paradigm with implications for obesity and osteoporosis...
- A novel spontaneous mutation of Irs1 in mice results in hyperinsulinemia, reduced growth, low bone mass and impaired adipogenesis
Victoria E DeMambro
The Jackson Laboratory, Bar Harbor, Maine 04609, USA
J Endocrinol 204:241-53. 2010
..Changes in the heterozygous Irs1(+)(/sml) mice raise the possibility that similar mutations in humans are associated with short stature or osteoporosis...
- A chromosomal inversion within a quantitative trait locus has a major effect on adipogenesis and osteoblastogenesis
Cheryl L Ackert Bicknell
The Jackson Laboratory, Bar Harbor, ME 04609, USA
Ann N Y Acad Sci 1116:291-305. 2007
..Rather, 6T demonstrates that disordered regulation of gene expression by genomic rearrangement can have a profound effect on a complex trait, such as BMD, and that genomic rearrangement can supersede the effects of various alleles...
- A circadian-regulated gene, Nocturnin, promotes adipogenesis by stimulating PPAR-gamma nuclear translocation
Masanobu Kawai
The Musculoskeletal Laboratory, Maine Medical Center Research Institute, Scarborough, ME 04074, USA
Proc Natl Acad Sci U S A 107:10508-13. 2010
..These data illustrate a unique mechanism whereby a nutrient-responsive gene influences BMSCs differentiation, adipogenesis, and ultimately body composition...
- Sprouty1 is a critical regulatory switch of mesenchymal stem cell lineage allocation
Sumithra Urs
Maine Medical Center Research Institute, 81 Research Dr, Scarborough, ME 04074, USA
FASEB J 24:3264-73. 2010
..Spry1 is a critical regulator of adipocyte differentiation and mesenchymal stem cell (MSC) lineage allocation, potentially acting through regulation of CEBP-beta and TAZ...
- The many facets of PPARgamma: novel insights for the skeleton
Masanobu Kawai
Maine Medical Center Research Institute, Scarborough, ME 04074, USA
Am J Physiol Endocrinol Metab 299:E3-9. 2010
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- Allelic differences in a quantitative trait locus affecting insulin-like growth factor-I impact skeletal acquisition and body composition
Clifford J Rosen
The Jackson Laboratory, Bar Harbor, Maine, USA
Pediatr Nephrol 20:255-60. 2005
..Lifelong changes in circulating and skeletal IGF-I may be relevant for the pathophysiology of several diseases, including chronic renal failure...
- Leptin's RIGHT turn to the brain stem
Clifford J Rosen
Maine Medical Center Research Institute, Scarborough, ME 04074, USA
Cell Metab 10:243-4. 2009
..The data from those studies strengthen the tenet that skeletal remodeling is intimately connected to central regulation of metabolism...
- Bone: adiposity and bone accrual-still an established paradigm?
Masanobu Kawai
Skeletal Research Laboratory, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074 7205, USA
Nat Rev Endocrinol 6:63-4. 2010
..A new study published in the Journal of Bone and Mineral Research challenges the basic framework of that tenet...
- Treatment with once-weekly alendronate 70 mg compared with once-weekly risedronate 35 mg in women with postmenopausal osteoporosis: a randomized double-blind study
Clifford J Rosen
Maine Center of Osteoporosis Research and Education and St Joseph Hospital, Bangor, Maine 04401, USA
J Bone Miner Res 20:141-51. 2005
..The greater antiresorptive effect of alendronate was seen as early as 3 months, and the tolerability profiles were similar...
- Insulin-like growth factor-I and bone: lessons from mice and men
Masanobu Kawai
Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074 7205, USA
Pediatr Nephrol 24:1277-85. 2009
..This review highlights recent findings that shed new light on the interaction of the IGF-I signaling pathway with other skeletal networks, and the role of IGF-I in the bone marrow milieu...
- Genetic dissection of mouse distal chromosome 1 reveals three linked BMD QTLs with sex-dependent regulation of bone phenotypes
Wesley G Beamer
The Jackson Laboratory, Bar Harbor, Maine, USA
J Bone Miner Res 22:1187-96. 2007
..The homologous relationship between distal mouse Chr 1 and human 1q21-24 offers the possibility of finding common regulatory genes for cortical and trabecular bone...
- Bone remodeling, energy metabolism, and the molecular clock
Clifford J Rosen
Maine Medical Center Research Institute, Scarborough, ME 04074, USA
Cell Metab 7:7-10. 2008
..These findings support a new paradigm concerning the regulation of bone remodeling and provide a foundation for novel approaches to preventing osteoporosis...
- From mouse to man: redefining the role of insulin-like growth factor-I in the acquisition of bone mass
Shoshana Yakar
The National Institutes of Health and The Jackson Laboratory and St Joseph Hospital, Bangor, Maine 04401, USA
Exp Biol Med (Maywood) 228:245-52. 2003
..The implications are far reaching and suggest that newer approaches for manipulating the IGF regulatory system may one day be useful as therapeutic adjuncts for the treatment of osteoporosis...
- A missense mutation in the mouse Col2a1 gene causes spondyloepiphyseal dysplasia congenita, hearing loss, and retinoschisis
Leah Rae Donahue
The Jackson Laboratory, Bar Harbor, Maine 04609, USA
J Bone Miner Res 18:1612-21. 2003
..In addition, SED patients have been identified with a similar molecular mutation in human COL2A1. This mouse model offers a useful tool for molecular and biological studies of bone development and pathology...
- Aging in inbred strains of mice: study design and interim report on median lifespans and circulating IGF1 levels
Rong Yuan
The Jackson Aging Center at The Jackson Laboratory, Bar Harbor, ME 04609, USA
Aging Cell 8:277-87. 2009
..53, P < 0.01). These results support the hypothesis that the IGF1 pathway plays a key role in regulating longevity in mice and indicates that common genetic mechanisms may exist for regulating IGF1 levels and lifespan...
- Quantitative trait loci for BMD in an SM/J by NZB/BlNJ intercross population and identification of Trps1 as a probable candidate gene
Naoki Ishimori
The Jackson Laboratory, Bar Harbor, Maine 04609, USA
J Bone Miner Res 23:1529-37. 2008
..This study shows the power of statistical modeling to resolve linked QTLs and the use of haplotype analysis in narrowing the list of candidates...
- Quantitative trait loci that determine BMD in C57BL/6J and 129S1/SvImJ inbred mice
Naoki Ishimori
The Jackson Laboratory, Bar Harbor, Maine 04609, USA
J Bone Miner Res 21:105-12. 2006
..To identify loci controlling BMD, we conducted a QTL analysis in a (B6 x 129) F2 population of mice. We report on additional QTLs and also narrow one QTL by combining the data from multiple crosses and through haplotype analysis...
- Bone density in ambulatory and immobile children
Krystyna Tuckerman
Eastern Maine Medical Center, Bangor, USA
J Clin Densitom 5:327-34. 2002
..When bone measurements were corrected for bone volume, there was no difference in bone density between healthy control subjects and immobile children with neuromuscular disease an unexpected result...
- Minireview: A skeleton in serotonin's closet?
Masanobu Kawai
Center for Translational Research, Maine Medical Center Research Institute, Scarborough, Maine 04074, USA
Endocrinology 151:4103-8. 2010
..In this brief review, we will summarize recent findings linking serotonin to the skeleton and discuss future directions for this new but challenging aspect of this multidimensional molecule...
- Chromosomal inversion discovered in C3H/HeJ mice
Ellen C Akeson
The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA
Genomics 87:311-3. 2006
..The inversion has been named In(6)1J (inversion Chr 6, Jackson 1)...
