骨髓脂肪组织与疾病相关性及机制的研究进展
|
摘要
骨强度不仅与骨密度(BMD)、骨微结构相关,还受骨髓微环境的影响。骨髓脂肪组织(MAT)与骨小梁、造血细胞、神经血管组织共同存在于骨髓腔中,对骨重建、骨髓造血、维持骨髓微环境的稳定起重要作用。近年研究表明,MAT可通过分泌脂联素等细胞因子参与介导代谢性疾病、血液系统肿瘤、癌症等疾病的发生发展,为疾病预防、治疗及监测提供了新的思路。本文拟对MAT生物学特性、影像学测量方法、MAT与疾病相关性及可能的作用机制予以综述。
Bone strength is not only related to bone mineral density(BMD) and bone microarchitecture but also affected by the bone marrow microenvironment. Marrow adipose tissue(MAT) coexists with trabecular bonehematopoietic cells, nerve fibers and blood vessels in the medullary cavity,which plays an important role in bone remodeling, bone marrow hematopoiesis, and maintaining the stability of the bone marrow microenvironment. Recent studies have shown that MAT can participate in the development of various diseases such as metabolic diseases, hematological cancers and solid tumors by secreting cytokines such as adiponectin, providing new ideas for disease prevention, treatment and monitoring. Herein we review the biological characteristics and imaging methods of MAT, the correlation between MAT and disease and underlying mechanism.
Bone strength is not only related to bone mineral density(BMD) and bone microarchitecture but also affected by the bone marrow microenvironment. Marrow adipose tissue(MAT) coexists with trabecular bonehematopoietic cells, nerve fibers and blood vessels in the medullary cavity,which plays an important role in bone remodeling, bone marrow hematopoiesis, and maintaining the stability of the bone marrow microenvironment. Recent studies have shown that MAT can participate in the development of various diseases such as metabolic diseases, hematological cancers and solid tumors by secreting cytokines such as adiponectin, providing new ideas for disease prevention, treatment and monitoring. Herein we review the biological characteristics and imaging methods of MAT, the correlation between MAT and disease and underlying mechanism.
引文
[1]Kim TY,Schafer AL.Diabetes and bone marrow adiposity[J].Curr Osteoporos Rep,2016,14(6):337-344.
[2]Veldhuis-Vlug AG,Rosen CJ.Clinical implications of bone marrow adiposity[J].J Intern Med,2018,283(2):121-139.
[3]Yeung DK,Griffith JF,Antonio GE,et al.Osteoporosis is associated with increased marrow fat content and decreased marrow fat unsaturation:a proton MR spectroscopy study[J].JMagn Reson Imaging,2005,22(2):279-285.
[4]de Araujo IM,Salmon CE,Nahas AK,et al.Marrow adipose tissue spectrum in obesity and type 2 diabetes mellitus[J].Eur J Endocrinol,2017,176(1):21-30.
[5]Tabe Y,Yamamoto S,Saitoh K,et al.Bone marrow adipocytes facilitate fatty acid oxidation activating ampk and a transcriptional network supporting survival of acute monocytic leukemia cells[J].Cancer Res,2017,77(6):1453-1464.
[6]Li G,Xu Z,Zhuang A,et al.Magnetic Resonance spectroscopy-detected change in marrow adiposity is strongly correlated to postmenopausal breast cancer risk[J].Clin Breast Cancer,2017,17(3):239-244.
[7]Scheller EL,Doucette CR,Learman BS,et al.Region-specific variation in the properties of skeletal adipocytes reveals regulated and constitutive marrow adipose tissues[J].Nat Commun,2015,6:7808.
[8]Li Z,Hardij J,Bagchi DP,et al.Development,regulation,metabolism and function of bone marrow adipose tissues[J].Bone,2018,110:134-140.
[9]Masamoto Y,Arai S,Sato T,et al.Adiponectin enhances quiescence exit of murine hematopoietic stem cells and hematopoietic recovery through mTORC1 potentiation[J].Stem Cells,2017,35(7):1835-1848.
[10]Gasparrini M,Rivas D,Elbaz A,et al.Differential expression of cytokines in subcutaneous and marrow fat of aging C57BL/6Jmice[J].Exp Gerontol,2009,44(9):613-618.
[11]Gunaratnam K,Vidal C,Gimble JM,et al.Mechanisms of palmitate-induced lipotoxicity in human osteoblasts[J].Endocrinology,2014,155(1):108-116.
[12]Rahman S,Lu Y,Czernik PJ,et al.Inducible brown adipose tissue,or beige fat,is anabolic for the skeleton[J].Endocrinology,2013,154(8):2687-2701.
[13]Fan Y,Hanai JI,Le PT,et al.Parathyroid hormone directs bone marrow mesenchymal cell fate[J].Cell Metab,2017,25(3):661-672.
[14]Shafat MS,Oellerich T,Mohr S,et al.Leukemic blasts program bone marrow adipocytes to generate a protumoral microenvironment[J].Blood,2017,129(10):1320-1332.
[15]Diedrich JD,Rajagurubandara E,Herroon MK,et al.Bone marrow adipocytes promote the Warburg phenotype in metastatic prostate tumors via HIF-1alpha activation[J].Oncotarget,2016,7(40):64854-64877.
[16]Singhal V,Bredella MA.Marrow adipose tissue imaging in humans[J].Bone,2019,118:69-76.
[17]Kricun M E.Red-yellow marrow conversion:its effect on the location of some solitary bone lesions[J].Skeletal Radiol,1985,14(1):10-19.
[18]Shen W,Chen J,Gantz M,et al.MRI-measured pelvic bone marrow adipose tissue is inversely related to DXA-measured bone mineral in younger and older adults[J].Eur J Clin Nutr,2012,66(9):983-988.
[19]Hamilton G,Middleton MS,Bydder M,et al.Effect of PRESSand STEAM sequences on magnetic resonance spectroscopic liver fat quantification[J].J Magn Reson Imaging,2009,30(1):145-152.
[20]Patsch JM,Li X,Baum T,et al.Bone marrow fat composition as a novel imaging biomarker in postmenopausal women with prevalent fragility fractures[J].J Bone Miner Res,2013,28(8):1721-1728.
[21]Karampinos DC,Melkus G,Baum T,et al.Bone marrow fat quantification in the presence of trabecular bone:initial comparison between water-fat imaging and single-voxel MRS[J].Magn Reson Med,2014,71(3):1158-1165.
[22]Yu EW,Greenblatt L,Eajazi A,et al.Marrow adipose tissue composition in adults with morbid obesity[J].Bone,2017,97:38-42.
[23]Karampinos DC,Ruschke S,Dieckmeyer M,et al.Modeling of T2*decay in vertebral bone marrow fat quantification[J].NMR Biomed,2015,28(11):1535-1542.
[24]祝乐群,李冠武,施丹,等.多回波化学位移编码水/脂MRI评估骨髓脂肪的可行性研究[J].实用放射学杂志,2018(2):283-286,295.
[25]Arentsen L,Yagi M,Takahashi Y,et al.Validation of marrow fat assessment using noninvasive imaging with histologic examination of human bone samples[J].Bone,2015,72:118-122.
[26]Chiro GD,Brooks RA,Kessler RM,et al.Tissue signatures with dual-energy computed tomography[J].Radiology,1979,131(2):521-523.
[27]Bredella MA,Torriani M,Ghomi RH,et al.Vertebral bone marrow fat is positively associated with visceral fat and inversely associated with IGF-1 in obese women[J].Obesity(Silver Spring),2011,19(1):49-53.
[28]Magome T,Froelich J,Takahashi Y,et al.Evaluation of functional marrow irradiation based on skeletal marrow composition obtained using dual-energy computed tomography[J].Int J Radiat Oncol Biol Phys,2016,96(3):679-687.
[29]Bredella MA,Daley SM,Kalra MK,et al.Marrow adipose tissue quantification of the lumbar spine by using dual-energy CTand Single-Voxel(1)H MR spectroscopy:a feasibility study[J].Radiology,2015,277(1):230-235.
[30]Ergen FB,Gulal G,Yildiz AE,et al.Fat fraction estimation of the vertebrae in females using the T2*-IDEAL technique in detection of reduced bone mineralization level:comparison with bone mineral densitometry[J].J Comput Assist Tomogr,2014,38(2):320-324.
[31]Wehrli FW,Hopkins JA,Hwang SN,et al.Cross-sectional study of osteopenia with quantitative MR imaging and bone densitometry[J].Radiology,2000,217(2):527-538.
[32]Griffith JF,Yeung DK,Antonio GE,et al.Vertebral marrow fat content and diffusion and perfusion indexes in women with varying bone density:MR evaluation[J].Radiology,2006,241(3):831-838.
[33]Akune T,Ohba S,Kamekura S,et al.PPARgamma insufficiency enhances osteogenesis through osteoblast formation from bone marrow progenitors[J].J Clin Invest,2004,113(6):846-855.
[34]Li J,Zhang N,Huang X,et al.Dexamethasone shifts bone marrow stromal cells from osteoblasts to adipocytes by C/EBPalpha promoter methylation[J].Cell Death Dis,2013,4:e832.
[35]Wei W,Dutchak PA,Wang X,et al.Fibroblast growth factor21 promotes bone loss by potentiating the effects of peroxisome proliferator-activated receptor gamma[J].Proc Natl Acad Sci USA,2012,109(8):3143-3148.
[36]Wend K,Wend P,Drew BG,et al.ERalpha regulates lipid metabolism in bone through ATGL and perilipin[J].J Cell Biochem,2013,114(6):1306-1314.
[37]Fairfield H,Falank C,Harris E,et al.The skeletal cell-derived molecule sclerostin drives bone marrow adipogenesis[J].J Cell Physiol,2018,233(2):1156-1167.
[38]Vestergaard P.Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes--a metaanalysis[J].Osteoporos Int,2007,18(4):427-444.
[39]Napoli N,Chandran M,Pierroz DD,et al.Mechanisms of diabetes mellitus-induced bone fragility[J].Nat Rev Endocrinol,2017,13(4):208-219.
[40]Abdalrahaman N,McComb C,Foster JE,et al.Deficits in trabecular bone microarchitecture in young women with type 1 diabetes mellitus[J].J Bone Miner Res,2015,30(8):1386-1393.
[41]Chen SC,Brooks R,Houskeeper J,et al.Metformin suppresses adipogenesis through both AMP-activated protein kinase(AMPK)-dependent and AMPK-independent mechanisms[J].Mol Cell Endocrinol,2017,440:57-68.
[42]Falank C,Fairfield H,Reagan MR.Signaling interplay between bone marrow adipose tissue and multiple myeloma cells[J].Front Endocrinol(Lausanne),2016,7:67.
[43]Robinson L,Micali N,Misra M.Eating disorders and bone metabolism in women[J].Curr Opin Pediatr,2017,29(4):488-496.
[44]Whitney DG,Singh H,Miller F,et al.Cortical bone deficit and fat infiltration of bone marrow and skeletal muscle in ambulatory children with mild spastic cerebral palsy[J].Bone,2017,94:90-97.
[45]Moorthi RN,Fadel W,Eckert GJ,et al.Bone marrow fat is increased in chronic kidney disease by magnetic resonance spectroscopy[J].Osteoporos Int,2015,26(6):1801-1807.
[2]Veldhuis-Vlug AG,Rosen CJ.Clinical implications of bone marrow adiposity[J].J Intern Med,2018,283(2):121-139.
[3]Yeung DK,Griffith JF,Antonio GE,et al.Osteoporosis is associated with increased marrow fat content and decreased marrow fat unsaturation:a proton MR spectroscopy study[J].JMagn Reson Imaging,2005,22(2):279-285.
[4]de Araujo IM,Salmon CE,Nahas AK,et al.Marrow adipose tissue spectrum in obesity and type 2 diabetes mellitus[J].Eur J Endocrinol,2017,176(1):21-30.
[5]Tabe Y,Yamamoto S,Saitoh K,et al.Bone marrow adipocytes facilitate fatty acid oxidation activating ampk and a transcriptional network supporting survival of acute monocytic leukemia cells[J].Cancer Res,2017,77(6):1453-1464.
[6]Li G,Xu Z,Zhuang A,et al.Magnetic Resonance spectroscopy-detected change in marrow adiposity is strongly correlated to postmenopausal breast cancer risk[J].Clin Breast Cancer,2017,17(3):239-244.
[7]Scheller EL,Doucette CR,Learman BS,et al.Region-specific variation in the properties of skeletal adipocytes reveals regulated and constitutive marrow adipose tissues[J].Nat Commun,2015,6:7808.
[8]Li Z,Hardij J,Bagchi DP,et al.Development,regulation,metabolism and function of bone marrow adipose tissues[J].Bone,2018,110:134-140.
[9]Masamoto Y,Arai S,Sato T,et al.Adiponectin enhances quiescence exit of murine hematopoietic stem cells and hematopoietic recovery through mTORC1 potentiation[J].Stem Cells,2017,35(7):1835-1848.
[10]Gasparrini M,Rivas D,Elbaz A,et al.Differential expression of cytokines in subcutaneous and marrow fat of aging C57BL/6Jmice[J].Exp Gerontol,2009,44(9):613-618.
[11]Gunaratnam K,Vidal C,Gimble JM,et al.Mechanisms of palmitate-induced lipotoxicity in human osteoblasts[J].Endocrinology,2014,155(1):108-116.
[12]Rahman S,Lu Y,Czernik PJ,et al.Inducible brown adipose tissue,or beige fat,is anabolic for the skeleton[J].Endocrinology,2013,154(8):2687-2701.
[13]Fan Y,Hanai JI,Le PT,et al.Parathyroid hormone directs bone marrow mesenchymal cell fate[J].Cell Metab,2017,25(3):661-672.
[14]Shafat MS,Oellerich T,Mohr S,et al.Leukemic blasts program bone marrow adipocytes to generate a protumoral microenvironment[J].Blood,2017,129(10):1320-1332.
[15]Diedrich JD,Rajagurubandara E,Herroon MK,et al.Bone marrow adipocytes promote the Warburg phenotype in metastatic prostate tumors via HIF-1alpha activation[J].Oncotarget,2016,7(40):64854-64877.
[16]Singhal V,Bredella MA.Marrow adipose tissue imaging in humans[J].Bone,2019,118:69-76.
[17]Kricun M E.Red-yellow marrow conversion:its effect on the location of some solitary bone lesions[J].Skeletal Radiol,1985,14(1):10-19.
[18]Shen W,Chen J,Gantz M,et al.MRI-measured pelvic bone marrow adipose tissue is inversely related to DXA-measured bone mineral in younger and older adults[J].Eur J Clin Nutr,2012,66(9):983-988.
[19]Hamilton G,Middleton MS,Bydder M,et al.Effect of PRESSand STEAM sequences on magnetic resonance spectroscopic liver fat quantification[J].J Magn Reson Imaging,2009,30(1):145-152.
[20]Patsch JM,Li X,Baum T,et al.Bone marrow fat composition as a novel imaging biomarker in postmenopausal women with prevalent fragility fractures[J].J Bone Miner Res,2013,28(8):1721-1728.
[21]Karampinos DC,Melkus G,Baum T,et al.Bone marrow fat quantification in the presence of trabecular bone:initial comparison between water-fat imaging and single-voxel MRS[J].Magn Reson Med,2014,71(3):1158-1165.
[22]Yu EW,Greenblatt L,Eajazi A,et al.Marrow adipose tissue composition in adults with morbid obesity[J].Bone,2017,97:38-42.
[23]Karampinos DC,Ruschke S,Dieckmeyer M,et al.Modeling of T2*decay in vertebral bone marrow fat quantification[J].NMR Biomed,2015,28(11):1535-1542.
[24]祝乐群,李冠武,施丹,等.多回波化学位移编码水/脂MRI评估骨髓脂肪的可行性研究[J].实用放射学杂志,2018(2):283-286,295.
[25]Arentsen L,Yagi M,Takahashi Y,et al.Validation of marrow fat assessment using noninvasive imaging with histologic examination of human bone samples[J].Bone,2015,72:118-122.
[26]Chiro GD,Brooks RA,Kessler RM,et al.Tissue signatures with dual-energy computed tomography[J].Radiology,1979,131(2):521-523.
[27]Bredella MA,Torriani M,Ghomi RH,et al.Vertebral bone marrow fat is positively associated with visceral fat and inversely associated with IGF-1 in obese women[J].Obesity(Silver Spring),2011,19(1):49-53.
[28]Magome T,Froelich J,Takahashi Y,et al.Evaluation of functional marrow irradiation based on skeletal marrow composition obtained using dual-energy computed tomography[J].Int J Radiat Oncol Biol Phys,2016,96(3):679-687.
[29]Bredella MA,Daley SM,Kalra MK,et al.Marrow adipose tissue quantification of the lumbar spine by using dual-energy CTand Single-Voxel(1)H MR spectroscopy:a feasibility study[J].Radiology,2015,277(1):230-235.
[30]Ergen FB,Gulal G,Yildiz AE,et al.Fat fraction estimation of the vertebrae in females using the T2*-IDEAL technique in detection of reduced bone mineralization level:comparison with bone mineral densitometry[J].J Comput Assist Tomogr,2014,38(2):320-324.
[31]Wehrli FW,Hopkins JA,Hwang SN,et al.Cross-sectional study of osteopenia with quantitative MR imaging and bone densitometry[J].Radiology,2000,217(2):527-538.
[32]Griffith JF,Yeung DK,Antonio GE,et al.Vertebral marrow fat content and diffusion and perfusion indexes in women with varying bone density:MR evaluation[J].Radiology,2006,241(3):831-838.
[33]Akune T,Ohba S,Kamekura S,et al.PPARgamma insufficiency enhances osteogenesis through osteoblast formation from bone marrow progenitors[J].J Clin Invest,2004,113(6):846-855.
[34]Li J,Zhang N,Huang X,et al.Dexamethasone shifts bone marrow stromal cells from osteoblasts to adipocytes by C/EBPalpha promoter methylation[J].Cell Death Dis,2013,4:e832.
[35]Wei W,Dutchak PA,Wang X,et al.Fibroblast growth factor21 promotes bone loss by potentiating the effects of peroxisome proliferator-activated receptor gamma[J].Proc Natl Acad Sci USA,2012,109(8):3143-3148.
[36]Wend K,Wend P,Drew BG,et al.ERalpha regulates lipid metabolism in bone through ATGL and perilipin[J].J Cell Biochem,2013,114(6):1306-1314.
[37]Fairfield H,Falank C,Harris E,et al.The skeletal cell-derived molecule sclerostin drives bone marrow adipogenesis[J].J Cell Physiol,2018,233(2):1156-1167.
[38]Vestergaard P.Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes--a metaanalysis[J].Osteoporos Int,2007,18(4):427-444.
[39]Napoli N,Chandran M,Pierroz DD,et al.Mechanisms of diabetes mellitus-induced bone fragility[J].Nat Rev Endocrinol,2017,13(4):208-219.
[40]Abdalrahaman N,McComb C,Foster JE,et al.Deficits in trabecular bone microarchitecture in young women with type 1 diabetes mellitus[J].J Bone Miner Res,2015,30(8):1386-1393.
[41]Chen SC,Brooks R,Houskeeper J,et al.Metformin suppresses adipogenesis through both AMP-activated protein kinase(AMPK)-dependent and AMPK-independent mechanisms[J].Mol Cell Endocrinol,2017,440:57-68.
[42]Falank C,Fairfield H,Reagan MR.Signaling interplay between bone marrow adipose tissue and multiple myeloma cells[J].Front Endocrinol(Lausanne),2016,7:67.
[43]Robinson L,Micali N,Misra M.Eating disorders and bone metabolism in women[J].Curr Opin Pediatr,2017,29(4):488-496.
[44]Whitney DG,Singh H,Miller F,et al.Cortical bone deficit and fat infiltration of bone marrow and skeletal muscle in ambulatory children with mild spastic cerebral palsy[J].Bone,2017,94:90-97.
[45]Moorthi RN,Fadel W,Eckert GJ,et al.Bone marrow fat is increased in chronic kidney disease by magnetic resonance spectroscopy[J].Osteoporos Int,2015,26(6):1801-1807.