Essential requirement of BMPs-2/4 for both osteoblast and osteoclast formation in murine bone marrow cultures from adult mice: Antagonism by noggin
Essential requirement of BMPs-2/4 for both osteoblast and osteoclast formation in murine bone marrow cultures from adult mice: Antagonism by noggin
复制标题
DOI：
10.1359/jbmr.2000.15.4.663
复制
发表时间：
2000-04-01
影响因子：
6.2
通讯作者：
Manolagas, SC
中科院分区：
文献类型：
--
作者：
Abe, E;Yamamoto, M;Manolagas, SC
迄今为止，骨形态发生蛋白（BMP）一直被认为参与胚胎骨骼发生和骨折愈合过程中诱导未定型祖细胞分化为成骨细胞的过程。我们已经验证了这样的假设：BMP 也参与出生后骨髓中发生的成骨细胞生成。为此，我们利用了 noggin 的特性，这是一种最近发现的蛋白质，可结合 BMP-2 和 -4 并阻止其作用。将人重组头蛋白添加到正常成年小鼠的骨髓细胞培养物中可以抑制成骨细胞和破骨细胞的形成；这些效应可被外源性 BMP-2 逆转。与这些发现一致的是，在这些原代培养物、骨髓源性基质/成骨细胞系以及小鼠成年全骨中检测到了 BMP-2 和 -4 以及 BMP-2/4 受体转录物和蛋白质；在所有这些制剂中也记录了头蛋白的表达。此外，添加抗头蛋白抗体导致成骨细胞祖细胞形成增加。这些发现表明，BMP-2和-4在出生后的骨髓中表达，并有助于维持成骨细胞和破骨细胞的持续供应；事实上，BMP-2/4 诱导的成骨细胞谱系定向是破骨细胞发育的先决条件。因此，BMP 可能与头蛋白和可能的其他拮抗剂保持平衡，可以提供其他输入（例如激素、生物力学等）作用的骨重塑速率的强直基线控制。
Bone morphogenetic proteins (BMPs) have been heretofore implicated in the induction of osteoblast differentiation from uncommitted progenitors during embryonic skeletogenesis and fracture healing. We have tested the hypothesis that BMPs are also involved in the osteoblastogenesis that takes place in the bone marrow in postnatal life. To do this, we took advantage of the properties of noggin, a recently discovered protein that binds BMP-2 and -4 and blocks their action. Addition of human recombinant noggin to bone marrow cell cultures from normal adult mice inhibited both osteoblast and osteoclast formation; these effects were reversed by exogenous BMP-2. Consistent with these findings, BMP-2 and -4 and BMP-2/4 receptor transcripts and proteins were detected in these primary cultures, in a bone marrow-derived stromal/osteoblastic cell line, as well as in murine adult whole bone; noggin expression was also documented in all these preparations. Moreover, addition of antinoggin antibody caused an increase in osteoblast progenitor formation. These findings suggest that BMP-2 and -4 are expressed in the bone marrow in postnatal life and serve to maintain the continuous supply of osteoblasts and osteoclasts; and that, in fact, BMP-2/4-induced commitment to the osteoblastic lineage is a prerequisite for osteoclast development. Hence, BMPs, perhaps in balance with noggin and possibly other antagonists, may provide the tonic baseline control of the rate of bone remodeling on which other inputs (e.g., hormonal, biomechanical, etc.) operate.