Bone morphogenic protein-2 signaling in human disc degeneration and correlation to the Pfirrmann MRI grading system.
Bone morphogenic protein-2 signaling in human disc degeneration and correlation to the Pfirrmann MRI grading system.
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DOI：
10.1016/j.spinee.2021.03.002
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发表时间：
2021-07
期刊：
影响因子：
--
通讯作者：
Mesfin A
中科院分区：
文献类型：
--
作者：
Hollenberg AM;Maqsoodi N;Phan A;Huber A;Jubril A;Baldwin AL;Yokogawa N;Eliseev RA;Mesfin A
椎间盘退变继发的背部和颈部疼痛是一个主要的公共健康负担。有必要治疗恢复椎间盘（IVD）的组成和功能。量化椎间盘退变手术患者IVD标本中ALK3、BMP-2、pSMAD1/5/8和MMP-13的表达，将IVD标本中ALK3、BMP-2、pSMAD1/5/8和MMP-13的表达与5级Pfirrmann MRI分级系统相关联，比较颈腰椎退变椎间盘标本中ALK3、BMP-2、pSMAD1/5/8和MMP-13的表达。免疫组织化学研究评估人类对照和退行性IVD标本中ALK3、BMP-2、pSMAD1/5/8和MMP-13的表达水平。从2015年1月至2017年8月在我院行椎间盘切除术和椎间融合术的手术患者中采集人类IVD标本。每位患者在手术前都进行了MRI检查。椎间盘退变程度根据Pfirrmann MRI 5级分级系统测量。患者分为两组：1)对照组（Pfirrmann分级为I-II级）和2)退行性组（Pfirrmann分级为III-V级）。收集的IVD标本制备组织学切片，免疫组化染色检测对照和退行性标本中ALK3、BMP-2、pSMAD1/5/8和MMP-13的表达水平。表达水平也与Pfirrmann标准相关。最后，根据退变标本的椎体水平进行分层，并比较退变的腰椎间盘和颈椎间盘之间的表达水平。52名患者入组；然而，由于数据集不完整，2例对照组和2例退行性变患者被排除在外。其余48例患者中，12例为对照，36例为退行性标本。退变标本BMP-2和pSMAD1/5/8表达水平升高（p < 0.0001）。Pfirrmann 3级（p = 0.0365）和4级（p = 0.0008）椎间盘的BMP-2表达明显高于2级椎间盘。Pfirrmann分级4级椎间盘中pSMAD1/5/8的表达高于分级2级椎间盘（p < 0.0001）。对照组与退变椎间盘间ALK3、MMP-13的表达差异无统计学意义（p < 0.05）。将退变标本按椎体水平分层，腰椎间盘和颈椎间盘的表达水平无显著差异（p < 0.05）。BMP-2和pSMAD1/5/8信号活性在人类退变标本中显著上调，而ALK3和MMP-13的表达没有显著变化。BMP-2和pSMAD1/5/8的表达水平与Pfirrmann MRI分级系统测量的椎间盘退变程度呈正相关。BMP-SMAD信号是恢复椎间盘退变情况下IVD组成和功能的有希望的治疗靶点。
Back and neck pain secondary to disc degeneration is a major public health burden. There is a need for therapeutic treatments to restore intervertebral disc (IVD) composition and function. To quantify ALK3, BMP-2, pSMAD1/5/8 and MMP-13 expression in IVD specimens collected from patients undergoing surgery for disc degeneration, to correlate ALK3, BMP-2, pSMAD1/5/8 and MMP-13 expression in IVD specimens to the 5-level Pfirrmann MRI grading system, and to compare ALK3, BMP-2, pSMAD1/5/8 and MMP-13 expression between cervical and lumbar degenerative disc specimens. An immunohistochemical study assessing ALK3, BMP-2, pSMAD1/5/8, and MMP-13 expression levels in human control and degenerative IVD specimens. Human IVD specimens were collected from surgical patients who underwent discectomy and interbody fusion at our institution between 1/2015 and 8/2017. Each patient underwent MRI prior to surgery. The degree of disc degeneration was measured according to the 5-level Pfirrmann MRI grading system. Patients were categorized into either the 1) control group (Pfirrmann grades I-II) or 2) degenerative group (Pfirrmann grades III-V). Histology slides of the collected IVD specimens were prepared and immunohistochemical staining was performed to assess ALK3, BMP-2, pSMAD1/5/8, and MMP-13 expression levels in the control and degenerative specimens. Expression levels were also correlated to the Pfirrmann criteria. Lastly, the degenerative specimens were stratified according to their vertebral level and expression levels between the degenerative lumbar and cervical discs were compared. Fifty-two patients were enrolled; however, 2 control and 2 degenerative patients were excluded due to incomplete data sets. Of the remaining 48 patients, there were 12 control and 36 degenerative specimens. Degenerative specimens had increased expression levels of BMP-2 (p = 0.0006) and pSMAD1/5/8 (p < 0.0001). Pfirrmann grade 3 (p = 0.0365) and grade 4 (p = 0.0008) discs had significantly higher BMP-2 expression as compared to grade 2 discs. Pfirrmann grade 4 discs had higher pSMAD1/5/8 expression as compared to grade 2 discs (p < 0.0001). There were no differences in ALK3 or MMP-13 expression between the control and degenerative discs (p > 0.05). Stratifying the degenerative specimens according to their vertebral level showed no significant differences in expression levels between the lumbar and cervical discs (p > 0.05). BMP-2 and pSMAD1/5/8 signaling activity was significantly upregulated in the human degenerative specimens, while ALK3 and MMP-13 expression were not significantly changed. The expression levels of BMP-2 and pSMAD1/5/8 correlate positively with the degree of disc degeneration measured according to the Pfirrmann MRI grading system. BMP-SMAD signaling represents a promising therapeutic target to restore IVD composition and function in the setting of disc degeneration.
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影响因子：
3.7
作者：
Förster M;Mahn F;Gockel U;Brosz M;Freynhagen R;Tölle TR;Baron R
通讯作者：
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影响因子：
3
作者：
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通讯作者：
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影响因子：
2.8
作者：
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通讯作者：
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影响因子：
168.9
作者：
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通讯作者：
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影响因子：
7.3
作者：
Le Maitre, CL;Freemont, AJ;Hoyland, JA
通讯作者：
Hoyland, JA