Functional heterogeneity of osteoclasts: matrix metalloproteinases participate in osteoclastic resorption of calvarial bone but not in resorption of long bone
Functional heterogeneity of osteoclasts: matrix metalloproteinases participate in osteoclastic resorption of calvarial bone but not in resorption of long bone
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DOI：
10.1096/fasebj.13.10.1219
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发表时间：
1999-07-01
期刊：
影响因子：
4.8
通讯作者：
Beertsen, W
中科院分区：
文献类型：
--
作者：
Everts, V;Korper, W;Beertsen, W
文献中的数据表明，在破骨细胞对骨的消化方面，骨骼中存在特定部位的差异。因此，我们研究了颅骨破骨细胞(膜内骨)的骨吸收是否与长骨破骨细胞(软骨内骨)的骨吸收不同。通过分析两类主要的蛋白水解酶--半胱氨酸蛋白酶(CPS)和基质金属蛋白酶(MMPs)的选择性低分子量抑制剂对骨吸收的影响，研究了这两类酶的参与情况。小鼠组织外植体(颅骨和长骨)以及从两个骨骼部位分离的兔破骨细胞随后种植在骨片上，在抑制剂的存在下进行培养，并分析吸收情况。用生化方法(CPS和MMPs)和酶组织化学法(CPS)检测组织块和破骨细胞中CP、组织蛋白B和K的活性以及MMPs的活性。我们发现颅骨的破骨细胞吸收依赖于CPS和MMPs的活性，而长骨的吸收依赖于CPS，而不是MMPs的活性。此外，长骨破骨细胞表达的组织蛋白酶B和组织蛋白酶K活性明显高于颅骨破骨细胞。从长骨分离的破骨细胞对牛头骨或皮质骨切片的吸收不受基质金属蛋白酶抑制剂的影响，而颅骨破骨细胞的吸收受到抑制。CP活性的抑制以相似的方式影响两组破骨细胞的吸收。我们的结论是，这是第一个表明颅骨破骨细胞和长骨破骨细胞在骨吸收活性方面存在显著差异的报告。颅骨破骨细胞的吸收主要取决于CPS和MMPs的活性，而长骨破骨细胞的吸收主要取决于CPS的活性。我们假设，功能不同的破骨细胞亚群，如这里描述的那些，来自不同的祖细胞集。
Data in the literature suggest that site-specific differences exist in the skeleton with respect to digestion of bone by osteoclasts. Therefore, we investigated whether bone resorption by calvarial osteoclasts (intramembranous bone) differs from resorption by long bone osteoclasts (endochondral bone). The involvement of two major classes of proteolytic enzymes, the cysteine proteinases (CPs) and matrix metalloproteinases (MMPs), was studied by analyzing the effects of selective low molecular weight inhibitors of these enzymes on bone resorption. Mouse tissue explants (calvariae and long bones) as well as rabbit osteoclasts, which had been isolated from both skeletal sites and subsequently seeded on bone slices, were cultured in the presence of inhibitors and resorption was analyzed. The activity of the CP cathepsins B and K and of MMPs was determined biochemically (CPs and MMPs) and enzyme histochemically (CPs) in explants and isolated osteoclasts. We show that osteoclastic resorption of calvarial bone depends on activity of both CPs and MMPs, whereas long bone resorption depends on CPs, but not on the activity of MMPs. Furthermore, significantly higher levels of cathepsin B and cathepsin K activities were expressed by long bone osteoclasts than by calvarial osteoclasts. Resorption of slices of bovine skull or cortical bone by osteoclasts isolated from long bones was not affected by MMP inhibitors, whereas resorption by calvarial osteoclasts was inhibited. Inhibition of CP activity affected the resorption by the two populations of osteoclasts in a similar way. We conclude that this is the first report to show that significant differences exist between osteoclasts of calvariae and long bones with respect to their bone resorbing activities. Resorption by calvarial osteoclasts depends on the activity of CPs and MMPs, whereas resorption by long bone osteoclasts depends primarily on the activity of CPs. We hypothesize that functionally different subpopulations of osteoclasts, such as those described here, originate from different sets of progenitors.