HB-EGF在骨骼生长过程中在间质基质细胞增殖和分化中的作用。,Journal of Bone and Mineral Research

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HB-EGF在骨骼生长过程中在间质基质细胞增殖和分化中的作用。
Journal of Bone and Mineral Research ( IF 5.1 ) Pub Date : 2018-12-14 , DOI: 10.1002/jbmr.3596
Ping Li ₁ , Qi Deng ₁ , Jiajia Liu ₁ , Jianshe Yan _{2,

3} , Zhanying Wei ₄ , Zhenlin Zhang ₄ , Huijuan Liu ₁ , Baojie Li ₁

Affiliation

HB-EGF是EGF超家族的成员，在发育和组织再生中起着重要作用。然而，其在骨骼干细胞以及骨骼发育和生长中的功能仍知之甚少。在这里，我们使用Cre / LoxP系统在Dermo1 +间充质基质细胞及其后代，包括软骨细胞和成骨细胞谱系细胞，以及骨髓基质细胞（BMSC）中消融或表达HB-EGF。Dermo1-Cre; HB-EGFf / f小鼠仅表现出适度的骨量增加，而Dermo1-HB-EGF小鼠则发展为进行性软骨发育不良，软骨瘤，类骨关节炎样关节缺损以及骨量和密度的损失，这可以通过使用EGFR抑制剂治疗得到缓解AG1478。在严重程度较低的软骨细胞特异性HB-EGF过表达（Col2-HB-EGF）小鼠中概括了软骨缺损。Dermo1-HB-EGF小鼠显示出增殖的增加，但软骨细胞和成骨细胞的分化却存在缺陷。HB-EGF通过Akt1和Erk途径促进BMSC增殖，但通过抑制Smad1 / 5/8激活抑制BMSC分化。但是，Dermo1-HB-EGF小鼠表现出正常的破骨细胞生成和骨吸收。这些结果揭示了自分泌或旁分泌HB-EGF在间充质基质细胞增殖和分化中的重要功能，并建议需要严格控制EGF信号传导以维持骨骼和关节软骨的完整性。©2018作者。Wiley Periodicals Inc.出版的《骨与矿物质研究杂志》HB-EGF通过Akt1和Erk途径促进BMSC增殖，但通过抑制Smad1 / 5/8激活抑制BMSC分化。但是，Dermo1-HB-EGF小鼠表现出正常的破骨细胞生成和骨吸收。这些结果揭示了自分泌或旁分泌HB-EGF在间充质基质细胞增殖和分化中的重要功能，并建议需要严格控制EGF信号传导以维持骨骼和关节软骨的完整性。©2018作者。Wiley Periodicals Inc.出版的《骨与矿物质研究杂志》HB-EGF通过Akt1和Erk途径促进BMSC增殖，但通过抑制Smad1 / 5/8激活抑制BMSC分化。但是，Dermo1-HB-EGF小鼠表现出正常的破骨细胞生成和骨吸收。这些结果揭示了自分泌或旁分泌HB-EGF在间充质基质细胞增殖和分化中的重要功能，并建议需要严格控制EGF信号传导以维持骨骼和关节软骨的完整性。©2018作者。Wiley Periodicals Inc.出版的《骨与矿物质研究杂志》这些结果揭示了自分泌或旁分泌HB-EGF在间充质基质细胞增殖和分化中的重要功能，并建议需要严格控制EGF信号传导以维持骨骼和关节软骨的完整性。©2018作者。Wiley Periodicals Inc.出版的《骨与矿物质研究杂志》这些结果揭示了自分泌或旁分泌HB-EGF在间充质基质细胞增殖和分化中的重要功能，并建议需要严格控制EGF信号传导以维持骨骼和关节软骨的完整性。©2018作者。Wiley Periodicals Inc.出版的《骨与矿物质研究杂志》

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Roles for HB-EGF in Mesenchymal Stromal Cell Proliferation and Differentiation During Skeletal Growth.

HB-EGF, a member of the EGF superfamily, plays important roles in development and tissue regeneration. However, its functions in skeletal stem cells and skeleton development and growth remain poorly understood. Here, we used the Cre/LoxP system to ablate or express HB-EGF in Dermo1+ mesenchymal stromal cells and their progenies, including chondrocytes and osteoblast lineage cells, and bone marrow stromal cells (BMSCs). Dermo1-Cre; HB-EGFf/f mice only showed a modest increase in bone mass, whereas Dermo1-HB-EGF mice developed progressive chondrodysplasia, chondroma, osteoarthritis-like joint defects, and loss of bone mass and density, which were alleviated by treatment with EGFR inhibitor AG1478. The cartilage defects were recapitulated in chondrocyte-specific HB-EGF overexpression (Col2-HB-EGF) mice with a lesser severity. Dermo1-HB-EGF mice showed an increase in proliferation but defects in differentiation of chondrocytes and osteoblasts. HB-EGF promoted BMSC proliferation via the Akt1 and Erk pathways but inhibited BMSC differentiation via restraining Smad1/5/8 activation. However, Dermo1-HB-EGF mice showed normal osteoclastogenesis and bone resorption. These results reveal an important function of autocrine or paracrine HB-EGF in mesenchymal stromal cell proliferation and differentiation and suggest that EGF signaling needs to be tightly controlled to maintain bone and articular cartilage integrity. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.

更新日期：2018-12-15

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