Blocking CCN2 preferentially inhibits osteoclastogenesis induced by repetitive high force bone loading.
Blocking CCN2 preferentially inhibits osteoclastogenesis induced by repetitive high force bone loading.
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DOI：
10.1080/03008207.2020.1788546
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发表时间：
2021-01
影响因子：
2.9
通讯作者：
Popoff SN
中科院分区：
文献类型：
--
作者：
Barbe MF;Amin M;Gingery A;Lambi AG;Popoff SN
我们最近发现，使用单克隆抗体（FG-3019）阻断CCN2信号可能是一种减少过度使用诱导的组织纤维化的新治疗策略。由于CCN2在破骨细胞形成中起作用，并且持续进行高重复高强度（HRHF）杠杆牵引任务会导致桡骨小梁骨体积的损失，因此我们在这里研究了阻断CCN2信号是否会降低执行HRHF任务3周的早期分解代谢作用。在执行HRHF任务前，对年轻成年雌性Sprague-Dawley大鼠进行开放性训练，以学习在高强度下拉扯，为期3周。然后，HRHF任务大鼠不进行治疗（HRHF未治疗），在任务第2周和第3周使用拮抗CCN2的单克隆抗体（HRHF+FG-3019）或IgG （HRHF+IgG）治疗，同时继续执行任务。非任务控制大鼠不接受治疗。在桡骨远端干骺端小梁中，HRHF治疗组和HRHF- igg组大鼠的成骨细胞数量和其他成骨指标均较对照组增加，但小梁骨体积减少，破骨细胞数量增加，血清CTX-1（骨吸收的血清生物标志物）升高。HRHF+FG-3019大鼠也显示出成骨细胞数量和骨形成的增加，但与HRHF未治疗和HRHF- igg大鼠相比，显示出更高的骨小梁体积，破骨细胞数量和血清CTX-1水平降低（与对照组相似）。HRHF负荷增加了每个任务组的骨形成，但阻断CCN2通过减少破骨细胞的数量和活性来抑制小梁骨分解代谢。
We recently found that blocking CCN2 signaling using a monoclonal antibody (FG-3019) may be a novel therapeutic strategy for reducing overuse-induced tissue fibrosis. Since CCN2 plays roles in osteoclastogenesis, and persistent performance of a high repetition high force (HRHF) lever pulling task results in a loss in trabecular bone volume in the radius, we examined here whether blocking CCN2 signaling would reduce the early catabolic effects of performing a HRHF task for 3 weeks. Young adult, female, Sprague-Dawley rats were operantly shaped to learn to pull at high force levels, before performing the HRHF task for 3 weeks. HRHF task rats were then left untreated (HRHF Untreated), treated in task weeks 2 and 3 with a monoclonal antibody that antagonizes CCN2 (HRHF+FG-3019), or treated with an IgG (HRHF+IgG), while continuing to perform the task. Non task control rats were left untreated. In metaphyseal trabeculae of the distal radius, HRHF Untreated and HRHF-IgG rats showed increased osteoblast numbers and other indices of bone formation, compared to controls, yet decreased trabecular bone volume, increased osteoclast numbers, and increased serum CTX-1 (a serum biomarker of bone resorption). HRHF+FG-3019 rats also showed increased osteoblast numbers and bone formation, but in contrast to HRHF Untreated and HRHF-IgG rats, showed higher trabecular bone volume, and reduced osteoclast numbers and serum CTX-1 levels (and statistically similar to Control levels). HRHF loading increased bone formation in each task group, yet blocking CCN2 dampened trabecular bone catabolism by reducing osteoclast numbers and activity.
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影响因子：
3.5
作者：
Gabriela Morales, Maria;Gutierrez, Jaime;Brandan, Enrique
通讯作者：
Brandan, Enrique
影响因子：
4.6
作者：
Ivkovic, S;Yoon, BS;Lyons, KM
通讯作者：
Lyons, KM
影响因子：
3.5
作者：
Gonzalez, David;Rebolledo, Daniela L.;Brandan, Enrique
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Brandan, Enrique
影响因子：
6.2
作者：
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通讯作者：
Barbe, MF
影响因子：
4.3
作者：
Avin, Keith G.;Bloomfield, Susan A.;Gross, Ted S.;Warden, Stuart J.
通讯作者：
Warden, Stuart J.