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New approaches to imaging of articular cartilage
S22
Abstracts / Bone 47 (2010) S15–S28
most of the previous literature can be dismissed. Recently some preliminary genome wide association studies of 100,000 SNPS from Japan and pooled GWAS of 550,000 from UK have added further candidates. The Asian derived genes VWF, Calm1, CILP did not replicate in Europeans, and their role is uncertain. However the major robust and significant finding across all populations is the GDF5 genethis replicated consistently and is also a gene for height- and is a skeletal development gene and may have a role in hip dysplasia. Larger GWAS studies are underway in Europe via the EU funded Treat-OA consortium (www.Treat-OA.eu) with access to over 20,000 cases and 40,000 controls and year as well as genes which influence biomarkers and progression rates. To date these meta-analyses have shown another definite gene locus in Chromosome 7- which has 5 possible functional candidates. So far Major genes for BMD have not been found to influence OA in meta-analyses. OA gene finding is proving more difficult than for BMD- this may be because of smaller populations or the heterogeneity of the phenotype. (www.treat-OA.eu). Disclosure of Interest: None declared Keywords: genomewide association studies, linkage, osteoarthritis doi:10.1016/j.bone.2010.04.023
IS23 New approaches to imaging of articular cartilage S. Majumdar⁎1 1 Radiology and Biomedical Imaging, University of California, San Francisco, United States The hyaline articular cartilage is composed of chondrocytes surrounded by a large extracellular matrix (ECM). The ECM is composed of water and two groups of macromolecules: proteoglycan (PG) and collagen fibers. These macromolecules restrict the motion of water protons. Changes to the ECM precede morphological changes in articular cartilage and may be early biomarkers of osteo-arthritis. ECM changes such as PG loss, may be reflected in measurements of: 1) T1ρ of water protons, 2) Delayed Gadolinium Delayed gadoliniumenhanced MRI of cartilage (dGEMRIC). Collagen content and orientation changes can be probed using T2 relaxation time measures. In vitro studies and validation of these methodologies have been widespread, and more recently in-vivo studies have also confirmed the potential for quantitative imaging for monitoring changes in the ECM. In vitro studies have evaluated the relationship between T1ρ relaxation time and the biochemical composition of cartilage. In vivo studies showed increased cartilage T1ρ values in OA subjects compared to controls. In addition to evaluating cartilage in patients with OA, T1ρ quantification techniques have been applied to cartilage in patients with acutely injured knees, who have a high risk of developing OA. In vitro imaging studies have evaluated the relationship between biochemistry of cartilage and T2 measurements. A recent in vitro study has shown that T2 relaxation time in human patellar cartilage is significantly correlated to Young's Modulus, suggesting that T2 quantification may predict the mechanical properties of cartilage. In vivo imaging studies have measured T2 relaxation time to evaluate the effects of gender, age, disease, activity level. Studies have measured T2 relaxation time to assess cartilage following cartilage repair. With these techniques and other emerging methodologies including Sodium imaging, and Glycosamin Concentration by Chemical Exchange Dependent Saturation Transfer gagCEST, the role of quantitative imaging in assessing early cartilage changes has tremendous clinical potential. Translating these methodologies to
the clinic clearly requires standardization of imaging, analysis protocols, commitments from the vendors for long term support of the acquisition sequences. Multi-center trials and testing of these tools in specific populations will enhance the role of MR imaging in Osteoarthritis and related disorders. Disclosure of Interest: None declared Keywords: None doi:10.1016/j.bone.2010.04.024
IS24 Hematopoietic stem cells and bone☆ G.B. Adams⁎1 1 Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, University of Southern California, Los Angeles, United States In the hematopoietic stem cell (HSC) niche it has been hypothesized that neighboring subsets of cells and extracellular substrates house stem cells and provide specialized functions to modulate self renewal and progeny production in vivo. Previously we have demonstrated that cells of the osteoblastic lineage play a key role in the adult bone marrow HSC niche and that specific targeting of this population leads to enhancement of HSC-based therapies. However, recent studies have suggested that global osteoblastic expansion is not sufficient to expand the HSC pool, and that there may actually be a role for osteoclastic regulation of HSC physiology. In addition, while hematopoiesis occurs in many bones, the regulation of the osteoclastic cells differs between bones that develop through endochondral ossification (long bones) and those that form through membranous ossification (flat bones). Therefore we have examined the role played by the niche component cells in these two distinct bones and whether these microenvironments have differing effects on the HSCs. Our findings will define the role of osteoclasts in the HSC niche in vivo and thus define the role played by these cells in HSC selfrenewal or differentiation. By defining these cellular participants, it may be possible to define the complexity of the niche and tease apart the systems directing stem cell behavior. Understanding all of these interactions may, therefore, yield both practical methods for manipulating stem cells and define a model for the impact of the microenvironment on mammalian stem cell physiology. Disclosure of Interest: None declared Keywords: hematopoiesis, stem cells doi:10.1016/j.bone.2010.04.025
IS25 Osteoblasts in hematopoiesis and lymphopoiesis☆ S.G. Emerson⁎1 1 Department of Biology, Haverford College, Haverford, United States Two key facts have long linked hematopoietic stem cell (HSC) differentiation to cells of the osteoblast-osteocyte lineage. First, hematopoietic stem cells require both adhesion-based and soluble polypeptide hormonal growth factors to survive and differentiate; and second, the major post-natal site of both myelopoiesis and early B lymphopoiesis is within the bone marrow. Until the 1990s, connections between osteogenesis and hematopoiesis were merely surmises. Studies over the past 15 years, however, have shown that: 1) HSC stimulatory function of osteoblasts is induced by the local
Abstracts / Bone 47 (2010) S15–S28
most of the previous literature can be dismissed. Recently some preliminary genome wide association studies of 100,000 SNPS from Japan and pooled GWAS of 550,000 from UK have added further candidates. The Asian derived genes VWF, Calm1, CILP did not replicate in Europeans, and their role is uncertain. However the major robust and significant finding across all populations is the GDF5 genethis replicated consistently and is also a gene for height- and is a skeletal development gene and may have a role in hip dysplasia. Larger GWAS studies are underway in Europe via the EU funded Treat-OA consortium (www.Treat-OA.eu) with access to over 20,000 cases and 40,000 controls and year as well as genes which influence biomarkers and progression rates. To date these meta-analyses have shown another definite gene locus in Chromosome 7- which has 5 possible functional candidates. So far Major genes for BMD have not been found to influence OA in meta-analyses. OA gene finding is proving more difficult than for BMD- this may be because of smaller populations or the heterogeneity of the phenotype. (www.treat-OA.eu). Disclosure of Interest: None declared Keywords: genomewide association studies, linkage, osteoarthritis doi:10.1016/j.bone.2010.04.023
IS23 New approaches to imaging of articular cartilage S. Majumdar⁎1 1 Radiology and Biomedical Imaging, University of California, San Francisco, United States The hyaline articular cartilage is composed of chondrocytes surrounded by a large extracellular matrix (ECM). The ECM is composed of water and two groups of macromolecules: proteoglycan (PG) and collagen fibers. These macromolecules restrict the motion of water protons. Changes to the ECM precede morphological changes in articular cartilage and may be early biomarkers of osteo-arthritis. ECM changes such as PG loss, may be reflected in measurements of: 1) T1ρ of water protons, 2) Delayed Gadolinium Delayed gadoliniumenhanced MRI of cartilage (dGEMRIC). Collagen content and orientation changes can be probed using T2 relaxation time measures. In vitro studies and validation of these methodologies have been widespread, and more recently in-vivo studies have also confirmed the potential for quantitative imaging for monitoring changes in the ECM. In vitro studies have evaluated the relationship between T1ρ relaxation time and the biochemical composition of cartilage. In vivo studies showed increased cartilage T1ρ values in OA subjects compared to controls. In addition to evaluating cartilage in patients with OA, T1ρ quantification techniques have been applied to cartilage in patients with acutely injured knees, who have a high risk of developing OA. In vitro imaging studies have evaluated the relationship between biochemistry of cartilage and T2 measurements. A recent in vitro study has shown that T2 relaxation time in human patellar cartilage is significantly correlated to Young's Modulus, suggesting that T2 quantification may predict the mechanical properties of cartilage. In vivo imaging studies have measured T2 relaxation time to evaluate the effects of gender, age, disease, activity level. Studies have measured T2 relaxation time to assess cartilage following cartilage repair. With these techniques and other emerging methodologies including Sodium imaging, and Glycosamin Concentration by Chemical Exchange Dependent Saturation Transfer gagCEST, the role of quantitative imaging in assessing early cartilage changes has tremendous clinical potential. Translating these methodologies to
the clinic clearly requires standardization of imaging, analysis protocols, commitments from the vendors for long term support of the acquisition sequences. Multi-center trials and testing of these tools in specific populations will enhance the role of MR imaging in Osteoarthritis and related disorders. Disclosure of Interest: None declared Keywords: None doi:10.1016/j.bone.2010.04.024
IS24 Hematopoietic stem cells and bone☆ G.B. Adams⁎1 1 Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, University of Southern California, Los Angeles, United States In the hematopoietic stem cell (HSC) niche it has been hypothesized that neighboring subsets of cells and extracellular substrates house stem cells and provide specialized functions to modulate self renewal and progeny production in vivo. Previously we have demonstrated that cells of the osteoblastic lineage play a key role in the adult bone marrow HSC niche and that specific targeting of this population leads to enhancement of HSC-based therapies. However, recent studies have suggested that global osteoblastic expansion is not sufficient to expand the HSC pool, and that there may actually be a role for osteoclastic regulation of HSC physiology. In addition, while hematopoiesis occurs in many bones, the regulation of the osteoclastic cells differs between bones that develop through endochondral ossification (long bones) and those that form through membranous ossification (flat bones). Therefore we have examined the role played by the niche component cells in these two distinct bones and whether these microenvironments have differing effects on the HSCs. Our findings will define the role of osteoclasts in the HSC niche in vivo and thus define the role played by these cells in HSC selfrenewal or differentiation. By defining these cellular participants, it may be possible to define the complexity of the niche and tease apart the systems directing stem cell behavior. Understanding all of these interactions may, therefore, yield both practical methods for manipulating stem cells and define a model for the impact of the microenvironment on mammalian stem cell physiology. Disclosure of Interest: None declared Keywords: hematopoiesis, stem cells doi:10.1016/j.bone.2010.04.025
IS25 Osteoblasts in hematopoiesis and lymphopoiesis☆ S.G. Emerson⁎1 1 Department of Biology, Haverford College, Haverford, United States Two key facts have long linked hematopoietic stem cell (HSC) differentiation to cells of the osteoblast-osteocyte lineage. First, hematopoietic stem cells require both adhesion-based and soluble polypeptide hormonal growth factors to survive and differentiate; and second, the major post-natal site of both myelopoiesis and early B lymphopoiesis is within the bone marrow. Until the 1990s, connections between osteogenesis and hematopoiesis were merely surmises. Studies over the past 15 years, however, have shown that: 1) HSC stimulatory function of osteoblasts is induced by the local