Adipocyte Accumulation in the Bone Marrow during Obesity and Aging Impairs Stem Cell-Based Hematopoietic and Bone Regeneration.
Adipocyte Accumulation in the Bone Marrow during Obesity and Aging Impairs Stem Cell-Based Hematopoietic and Bone Regeneration.
复制标题
DOI：
10.1016/j.stem.2017.02.009
复制
发表时间：
2017-06-01
期刊：
影响因子：
23.9
通讯作者：
Schulz TJ
中科院分区：
文献类型：
--
作者：
Ambrosi TH;Scialdone A;Graja A;Gohlke S;Jank AM;Bocian C;Woelk L;Fan H;Logan DW;Schürmann A;Saraiva LR;Schulz TJ
衰老和肥胖诱导骨髓腔异位脂肪细胞积聚。这一过程被认为会损害成骨和造血再生。在这里，我们详细说明了骨的成脂和成骨谱系的细胞特性。虽然衰老损害成骨谱系，但高脂饮食喂养激活了成脂谱系的扩张，这一效应在老年动物中显著增强。我们进一步描述了一种具有干细胞样特征的间充质亚群，其产生两种谱系，并且同时通过促进致死性照射后的竞争性再增殖而充当造血生态位的主要组成部分。相反，定向于脂肪细胞谱系的骨驻留细胞可能通过产生过量的二肽基肽酶-4（一种作为糖尿病治疗靶点的蛋白酶）来抑制造血和骨愈合。这些研究描绘了骨驻留脂肪细胞谱系的分子身份，并确定其参与骨和造血再生的年龄依赖性功能障碍。干细胞样群体在骨中产生成脂和成骨谱系衰老和高脂饮食特异性地促进成脂谱系的扩增多能细胞促进和成脂细胞减少造血重建成脂细胞抑制骨折修复，其通过DPP 4失活恢复Ambrosi，Schulz及其同事定义了一种干细胞样群体，其产生成骨后代并促进造血重建。衰老和高脂饮食重新编程间充质谱系，优先产生脂肪细胞，损害重建和骨折愈合。骨组织修复通过DPP 4抑制完全恢复。
Aging and obesity induce ectopic adipocyte accumulation in bone marrow cavities. This process is thought to impair osteogenic and hematopoietic regeneration. Here we specify the cellular identities of the adipogenic and osteogenic lineages of the bone. While aging impairs the osteogenic lineage, high-fat diet feeding activates expansion of the adipogenic lineage, an effect that is significantly enhanced in aged animals. We further describe a mesenchymal sub-population with stem cell-like characteristics that gives rise to both lineages and, at the same time, acts as a principal component of the hematopoietic niche by promoting competitive repopulation following lethal irradiation. Conversely, bone-resident cells committed to the adipocytic lineage inhibit hematopoiesis and bone healing, potentially by producing excessive amounts of Dipeptidyl peptidase-4, a protease that is a target of diabetes therapies. These studies delineate the molecular identity of the bone-resident adipocytic lineage, and they establish its involvement in age-dependent dysfunction of bone and hematopoietic regeneration. A stem cell-like population produces adipogenic and osteogenic lineages in bone Aging and high-fat diet specifically promote expansion of the adipogenic lineage Multipotent cells promote and adipogenic cells reduce hematopoietic reconstitution Adipogenic cells inhibit fracture repair, which is restored by DPP4 inactivation Ambrosi, Schulz, and colleagues define a stem cell-like population that gives rise to osteogenic progeny and promotes hematopoietic reconstitution. Aging and high-fat diet reprogram the mesenchymal lineage to preferentially give rise to adipogenic cells that impair reconstitution and bone fracture healing. Bone tissue repair is fully restored by DPP4 inhibition.