Mesenchymal stem cell surface antigen SB-10 corresponds to activated leukocyte cell adhesion molecule and is involved in osteogenic differentiation

Mesenchymal stem cell surface antigen SB-10 corresponds to activated leukocyte cell adhesion molecule and is involved in osteogenic differentiation
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DOI:
10.1359/jbmr.1998.13.4.655
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发表时间:
1998-04-01
影响因子:
6.2
通讯作者:
Barry, FP
Barry, FP
中科院分区:
医学1区
文献类型:
--
作者:
Bruder, SP;Ricalton, NS;Barry, FP

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骨髓中含有少量间充质干细胞(MSCs),其能够产生多种中胚层组织,包括骨、软骨、肌腱、肌肉和脂肪。单克隆抗体SB - 10所识别的细胞表面抗原在人MSCs上表达,但在其分化发育过程中会丢失。在此我们报道了SB - 10抗原的免疫纯化及其被鉴定为活化白细胞 - 细胞黏附分子(ALCAM)。质谱分析确定ALCAM的分子量为80303 ± 193道尔顿,并且它具有17763 ± 237道尔顿的N - 连接寡糖取代基。从MSCs表达文库中对全长cDNA进行分子克隆,证明其核苷酸序列与ALCAM相同。我们还在大鼠、兔和犬的MSCs中鉴定出ALCAM同源物,它们各自的肽序列与人ALCAM的同一性超过90%。在体外进行成骨分化的人MSCs中加入抗体SB - 10 F - ab片段加速了这一过程,从而暗示了ALCAM在骨形态发生过程中的作用,并将ALCAM列入参与成骨的细胞黏附分子组中。总之,这些结果提供了证据,表明ALCAM在整个系统发育树的多个物种的间充质组织分化中起着关键作用。
Bone marrow contains a rare population of mesenchymal stem cells (MSCs) capable of giving rise to multiple mesodermal tissues including bone, cartilage, tendon, muscle, and fat. The cell surface antigen recognized by monoclonal antibody SB-10 is expressed on human MSCs but is lost during their developmental progression into differentiated phenotypes. Here we report on the immunopurification of the SB-10 antigen and its identification as activated leukocyte-cell adhesion molecule (ALCAM). Mass spectrometry establishes that the molecular mass of ALCAM is 80,303 +/- 193 Da and that it possesses 17,763 +/- 237 Da of N-linked oligosaccharide substituents. Molecular cloning of a full-length cDNA from a MSC expression library demonstrates nucleotide sequence identity with ALCAM. We also identified ALCAM homologs in rat, rabbit, and canine MSCs, each of which is over 90% identical to human ALCAM in their peptide sequence. The addition of antibody SB-10 F-ab fragments to human MSCs undergoing osteogenic differentiation in vitro accelerated the process, thereby implicating a role for ALCAM during bone morphogenesis and adding ALCAM to the group of cell adhesion molecules involved in osteogenesis. Together, these results provide evidence that ALCAM plays a critical role in the differentiation of mesenchymal tissues in multiple species across the phylogenetic tree.