Secreted phosphoprotein 24 kD (Spp24) and Spp14 affect TGF-β induced bone formation differently.
Secreted phosphoprotein 24 kD (Spp24) and Spp14 affect TGF-β induced bone formation differently.
复制标题
DOI：
10.1371/journal.pone.0072645
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Murray SS
中科院分区：
文献类型：
--
作者：
Tian H;Bi X;Li CS;Zhao KW;Brochmann EJ;Montgomery SR;Aghdasi B;Chen D;Daubs MD;Wang JC;Murray SS
转化生长因子-β（TGF-β）和骨形态发生蛋白（BMP）在指导骨生长、修复和转换方面具有相反但互补的功能。两者都存在于骨基质中。与这些生长因子结合并影响其活性的蛋白质将决定生长因子的相对丰度，从而调节骨形成。分泌型磷蛋白24 kD（Spp24）是一种骨基质蛋白，已被证明与BMP结合并影响BMP的活性。Spp24的富含精氨酸的羧基末端被蛋白水解处理以产生另外三种可预测的截短产物（Spp18.1、Spp16.0和Spp14.5）。在这项工作中，我们报告了通过表面等离子体共振获得的动力学数据表明，Spp24和三个C-末端截短产物都以与BMP-2相似但略低的亲和力结合TGF-β 1和TGF-β 2;与BMP-2的情况一样，Spp24的全长（FL）形式以比截短产物更高的亲和力结合TGF-β; FL-Spp 24抑制TGF-β 2诱导的体内骨形成，但Spp 14.5不抑制;且FL-Spp 24或Spp 14.5与TGF-β 2的体内共施用与注射部位存在的软骨量相对于新骨的减少有关。这一发现与体内低剂量TGF-β给药比高剂量TGF-β给药与更大的骨形成相关的观察结果一致，并表明Spp24及其截短产物的一个功能是下调骨生长和发育期间的局部TGF-β活性或可用性。与Spp24蛋白和BMP的相互作用相比，Spp24蛋白和TGF-β之间的相互作用的相似性和差异对于骨代谢的调节和对于骨骼疾病的工程化治疗蛋白具有重要意义。
Transforming growth factor-β (TGF-β) and bone morphogenetic proteins (BMPs) have opposing but complementary functions in directing bone growth, repair, and turnover. Both are found in the bone matrix. Proteins that bind to and affect the activity of these growth factors will determine the relative abundance of the growth factors and, therefore, regulate bone formation. Secreted phosphoprotein 24 kD (Spp24) is a bone matrix protein that has been demonstrated to bind to and affect the activity of BMPs. The arginine-rich carboxy terminus of Spp24 is proteolytically processed to produce three other predictable truncation products (Spp18.1, Spp16.0, and Spp14.5). In this work, we report that kinetic data obtained by surface plasmon resonance demonstrate that Spp24 and the three C-terminal truncation products all bind to TGF-β1 and TGF-β2 with a similar but somewhat less affinity than they bind BMP-2; that, as in the case of BMP-2, the full-length (FL) form of Spp24 binds TGF-β with greater affinity than do the truncation products; that FL-Spp24 inhibits TGF-β2 induced bone formation in vivo, but Spp14.5 does not; and that co-administration of FL-Spp24 or Spp14.5 with TGF-β2 in vivo is associated with a reduction in the amount of cartilage, relative to new bone, present at the site of injection. This finding is consistent with the observation that low-dose TGF-β administration in vivo is associated with greater bone formation than high-dose TGF-β administration, and suggests that one function of Spp24 and its truncation products is to down-regulate local TGF-β activity or availability during bone growth and development. The similarities and differences of the interactions between Spp24 proteins and TGF-β compared to the interaction of the Spp24 proteins and BMPs have significant implications with respect to the regulation of bone metabolism and with respect to engineering therapeutic proteins for skeletal disorders.
登录
查看更多内容
影响因子：
5.7
作者：
Boesen, CC;Radaev, S;Sun, PD
通讯作者：
Sun, PD
影响因子：
2.8
作者：
Sintuu, Chananit;Murray, Samuel S.;Brochmann, Elsa J.
通讯作者：
Brochmann, Elsa J.
成骨细胞中 TGF-β2 表达增加会导致骨质疏松症样表型。
DOI：
10.1083/jcb.132.1.195
发表时间：
1996-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Erlebacher A;Derynck R
通讯作者：
Derynck R
影响因子：
2.8
作者：
Behnam, K;Phillips, ML;Murray, SS
通讯作者：
Murray, SS
影响因子：
3.5
作者：
Guimond, A;Sulea, T;O'Connor-McCourt, MD
通讯作者：
O'Connor-McCourt, MD