Osteoclasts secrete osteopontin into resorption lacunae during bone resorption
Osteoclasts secrete osteopontin into resorption lacunae during bone resorption
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DOI：
10.1007/s00418-019-01770-y
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发表时间：
2019-06-01
影响因子：
2.3
通讯作者：
Lehenkari, Petri
中科院分区：
文献类型：
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作者：
Luukkonen, Jani;Hilli, Meeri;Lehenkari, Petri
骨桥蛋白（OPN）是一种位于骨中的非胶原细胞外唾液化糖蛋白。它被认为是在骨吸收过程中破骨细胞附着在骨上的关键成分之一。在这项研究中，我们利用电子显微镜和质谱技术对吸收腔隙中发现的OPN和其他糖蛋白进行了表征，以证实破骨细胞在OPN分泌中的作用。此外，我们还研究了吸收坑的糖基表位以及不同糖基表位对破骨细胞分化和功能的影响。通过免疫组织化学检查骨关节炎股骨头，发现OPN存在于体内骨代谢增加的区域。我们的研究结果表明，人类破骨细胞将OPN分泌到天然人骨和缺乏天然OPN的碳化羟基磷灰石的吸收腔隙中。在实验条件下，OPN与骨关节炎骨的骨转换升高有关。我们的数据进一步证实，破骨细胞将OPN分泌到吸收坑中，在那里它可能作为随后骨形成的趋化因子发挥作用。我们发现α 2,3-和α 2,6-链唾液酸在破骨细胞分化过程中起作用。OPN是具有上述两种唾液残基的蛋白质之一，因此我们提出去唾液化可以影响骨中的破骨细胞分化。
Osteopontin (OPN) is a non-collagenous extracellular sialylated glycoprotein located in bone. It is believed to be one of the key components in osteoclast attachment to bone during resorption. In this study, we characterized OPN and other glycoproteins found in the resorption lacunae to confirm the role of osteoclasts in OPN secretion using electron microscopy and mass spectrometry. Additionally, we examined the glycan epitopes of resorption pits and the effects of different glycan epitopes on the differentiation and function of osteoclasts. Osteoarthritic femoral heads were examined by immunohistochemistry to reveal the presence of OPN in areas of increased bone metabolism in vivo. Our results demonstrate that human osteoclasts secrete OPN into resorption lacunae on native human bone and on carbonated hydroxyapatite devoid of natural OPN. OPN is associated with an elevated bone turnover in osteoarthritic bone under experimental conditions. Our data further confirm that osteoclasts secrete OPN into the resorption pit where it may function as a chemokine for subsequent bone formation. We show that alpha 2,3- and alpha 2,6-linked sialic acids have a role in the process of osteoclast differentiation. OPN is one of the proteins that has both of the above sialic residues, hence we propose that de-sialylation can effect osteoclast differentiation in bone.