Matrix metalloproteinase-13 is required for osteocytic perilacunar remodeling and maintains bone fracture resistance.
Matrix metalloproteinase-13 is required for osteocytic perilacunar remodeling and maintains bone fracture resistance.
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DOI：
10.1002/jbmr.1646
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发表时间：
2012-09
影响因子：
6.2
通讯作者：
Alliston, Tamara
中科院分区：
文献类型：
--
作者：
Tang, Simon Y.;Herber, Ralf-Peter;Ho, Sunita P.;Alliston, Tamara
关键词：
像骨量一样，骨质量在发育过程中被指定，在出生后被积极维持，并被疾病破坏。成骨细胞、破骨细胞和骨细胞在骨量调节中的作用越来越明确。然而，骨质量调控的细胞和分子机制尚不清楚。重塑骨细胞外基质的蛋白质，如胶原降解基质金属蛋白酶(MMP)-13，可能是调节骨质量的候选者。使用MMP-13缺陷小鼠，我们研究了MMP-13在骨基质重塑和维持以及随后的骨折抵抗中的作用。在缺乏mmp -13的胫骨骨干中，我们观察到非酶交联升高和高矿化、胶原蛋白破坏和小管畸形的同心区。这些缺陷局限于相同的中皮质骨区域，骨细胞腔隙和骨小管表现出MMP-13和抗酒石酸酸性磷酸酶（TRAP）的表达，以及骨细胞标记物硬化蛋白。尽管破骨细胞和成骨细胞功能正常，但动态组织形态测量显示，MMP-13−/−骨中骨细胞腔隙的重塑受损。对正常和哺乳期条件下的MMP-13 - / -小鼠及其野生型仔鼠的分析表明，MMP-13不仅是哺乳期诱导的骨细胞腔旁重构所必需的，而且也是维持骨质量所必需的。MMP-13的缺失，以及由此导致的骨腔周围重构和基质组织缺陷，损害了MMP-13 - / -骨断裂韧性和屈服后行为。综上所述，这些发现表明中皮质骨基质的骨细胞腔旁重构需要MMP-13，并且对维持骨质量至关重要。
Like bone mass, bone quality is specified in development, actively maintained post-natally, and disrupted by disease. The roles of osteoblasts, osteoclasts, and osteocytes in the regulation of bone mass are increasingly well defined. However, the cellular and molecular mechanisms by which bone quality is regulated remain unclear. Proteins that remodel bone extracellular matrix, such as the collagen-degrading matrix metalloproteinase (MMP)-13, are likely candidates that regulate bone quality. Using MMP-13 deficient mice, we examined the role of MMP-13 in the remodeling and maintenance of bone matrix and subsequent fracture resistance. Throughout the diaphysis of MMP-13-deficient tibiae, we observed elevated nonenzymatic crosslinking and concentric regions of hypermineralization, collagen disorganization, and canalicular malformation. These defects localize to the same mid-cortical bone regions where osteocyte lacunae and canaliculi exhibit MMP-13 and tartrate-resistant acid phosphatase (TRAP) expression, as well as the osteocyte marker Sclerostin. Despite otherwise normal measures of osteoclast and osteoblast function, dynamic histomorphometry revealed that remodeling of osteocyte lacunae is impaired in MMP-13−/− bone. Analysis of MMP-13−/− mice and their wild-type littermates in normal and lactating conditions showed that MMP-13 is not only required for lactation-induced osteocyte perilacunar remodeling, but also for the maintenance of bone quality. The loss of MMP-13, and the resulting defects in perilacunar remodeling and matrix organization, compromise MMP-13−/− bone fracture toughness and post-yield behavior. Taken together, these findings demonstrate that osteocyte perilacunar remodeling of mid-cortical bone matrix requires MMP-13 and is essential for the maintenance of bone quality.
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