Matrix metalloproteinase 13-deficient mice are resistant to osteoarthritic cartilage erosion but not chondrocyte hypertrophy or osteophyte development.
Matrix metalloproteinase 13-deficient mice are resistant to osteoarthritic cartilage erosion but not chondrocyte hypertrophy or osteophyte development.
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DOI：
10.1002/art.25002
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发表时间：
2009-12
影响因子：
--
通讯作者：
Thompson, E. W.
中科院分区：
文献类型：
--
作者：
Little, C. B.;Barai, A.;Burkhardt, D.;Smith, S. M.;Fosang, A. J.;Werb, Z.;Shah, M.;Thompson, E. W.
探讨基质金属蛋白酶（MMP）-13/胶原酶-3在骨关节炎（OA）中的作用。比较MMP-13敲除（KO）和野生型（WT）小鼠膝关节中手术诱导的OA。对股骨和胫骨软骨聚集蛋白聚糖损失（0-3）、侵蚀（0-7）和软骨细胞肥大（0-1）以及骨赘大小（0-3）和成熟度（0-3）进行组织学评分。对连续切片进行X型胶原和MMP产生的聚集蛋白聚糖新表位DIPEN染色。手术后，在WT小鼠中，胫骨中的聚集蛋白聚糖损失和软骨侵蚀比股骨更严重（p<0.01），并且胫骨软骨侵蚀随时间增加（p<0.05）。软骨性骨赘在4周时出现，并经历骨化，其大小和成熟度在8周时增加（p<0.01）。在4周时，聚集蛋白聚糖损失或软骨侵蚀的基因型之间没有差异。在8周时，KO小鼠中的胫骨软骨侵蚀小于WT（p<0.02）。KO组4周时软骨性骨赘较大（p<0.01），但8周时骨赘成熟度和大小与WT无差异。WT和KO关节中均出现关节软骨细胞肥大，X型胶原和DIPEN染色阳性。这些研究已经证实，小鼠实验性OA中的结构性软骨损伤依赖于MMP-13活性。在该模型中，软骨细胞肥大不受MMP-13活性的调节，其本身也不会导致软骨侵蚀。MMP-13缺乏可在聚集蛋白聚糖耗尽的情况下抑制软骨侵蚀，支持用MMP-13抑制剂对已建立的OA进行治疗性干预的潜力。
To investigate the role of matrix metalloproteinase (MMP)-13/collagenase-3 in osteoarthritis (OA). Surgically-induced OA in knees of MMP-13 knock out (KO) and wild type (WT) mice was compared. Femoral and tibial cartilage aggrecan loss (0–3), erosion (0–7) and chondrocyte hypertrophy (0–1), as well as osteophyte size (0–3) and maturity (0–3) were histologically scored. Serial sections were stained for collagen type X and the MMP-generated aggrecan neo-epitope DIPEN. Following surgery, aggrecan loss and cartilage erosion were more severe in the tibia than femur (p<0.01) and tibial cartilage erosion increased with time (p<0.05) in WT mice. Cartilaginous osteophytes were present at 4 weeks and underwent ossification, with size and maturity increasing by 8 weeks (p<0.01). There was no difference between genotypes in aggrecan loss or cartilage erosion at 4 weeks. Tibial cartilage erosion in KO mice was less than WT at 8 weeks (p<0.02). Cartilaginous osteophytes were larger in KO at 4 weeks (p<0.01), but by 8 weeks osteophyte maturity and size were no different from WT. Articular chondrocyte hypertrophy with positive type X collagen and DIPEN staining occurred in both WT and KO joints. These studies have confirmed that structural cartilage damage in mouse experimental OA is dependent on MMP-13 activity. Chondrocyte hypertrophy is not regulated by MMP-13 activity in this model and does not in itself lead to cartilage erosion. MMP-13 deficiency can inhibit cartilage erosion in the presence of aggrecan depletion, supporting the potential for therapeutic intervention in established OA with MMP-13 inhibitors.
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影响因子：
4.9
作者：
Krzeski, Piotr;Buckland-Wright, Chris;Spector, Tim D.
通讯作者：
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影响因子：
6.9
作者：
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通讯作者：
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DOI：
10.1016/j.bbrc.2006.12.234
发表时间：
2007-03-23
影响因子：
3.1
作者：
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通讯作者：
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影响因子：
7
作者：
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通讯作者：
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金属蛋白酶及其抑制剂在滑膜和软骨中的表达分析。
影响因子：
4.9
作者：
Davidson, Rose K;Waters, Jasmine G;Kevorkian, Lara;Darrah, Clare;Cooper, Adele;Donell, Simon T;Clark, Ian M
通讯作者：
Clark, Ian M