Dyment N A, Hagiwara Y, Jiang X, Huang J, Adams D J, Rowe D W
Center for Regenerative Medicine and Skeletal Development, School of Dental Medicine and Department of Orthopaedic Surgery, New England Musculoskeletal Institute, University of Connecticut Health Center, Farmington, CT 06032, USA.
Center for Regenerative Medicine and Skeletal Development, School of Dental Medicine and Department of Orthopaedic Surgery, New England Musculoskeletal Institute, University of Connecticut Health Center, Farmington, CT 06032, USA; Department of Orthopedic Surgery, Nippon Medical School Hospital, Tokyo 113, Japan.
Osteoarthritis Cartilage. 2015 Jun;23(6):996-1006. doi: 10.1016/j.joca.2015.01.017. Epub 2015 Feb 11.
A major challenge to understanding osteoarthritis (OA) pathology is identifying the cellular events that precede the onset of cartilage damage. The objective of this study is to determine the effect of joint destabilization on early changes to fibrocartilage in the joint.
DESIGN/METHODS: The anterior cruciate ligament was transected in collagen reporter mice (Col1CFP and ColXRFP). Mineralization labels were given every 2 weeks to measure new mineralized cartilage apposition. Novel fluorescent histology of mineralized tissue was used to characterize the changes in fibrocartilage at 2 and 4 weeks post-injury.
Changes in fibrocartilaginous structures of the joint occur as early as 2 weeks after injury and are well developed by 4 weeks. The alterations are seen in multiple entheses and in the medial surface of the femoral and tibial condyles. In the responding entheses, mineral apposition towards the ligament midsubstance results in thickening of the mineralize fibrocartilage. These changes are associated with increases in ColX-RFP, Col1-CFP reporter activity and alkaline phosphatase enzyme activity. Mineral apposition also occurs in the fibrocartilage of the non-articular regions of the medial condyles by 2 weeks and develops into osteophytes by 4 weeks post-injury. An unexpected observation is punctate expression of tartrate resistant acid phosphatase activity in unmineralized fibrochondrocytes adjacent to active appositional mineralization.
These observations suggest that fibrocartilage activates prior to degradation of the articular cartilage. Thus clinical and histological imaging of fibrocartilage may be an earlier indicator of disease initiation and may indicate a more appropriate time to start preventative treatment.
理解骨关节炎（OA）病理的一个主要挑战是确定软骨损伤发生之前的细胞事件。本研究的目的是确定关节失稳对关节内纤维软骨早期变化的影响。
设计/方法：在胶原蛋白报告基因小鼠（Col1CFP和ColXRFP）中切断前交叉韧带。每2周给予矿化标记物以测量新的矿化软骨附着情况。利用矿化组织的新型荧光组织学方法来表征损伤后2周和4周时纤维软骨的变化。
关节纤维软骨结构的变化早在损伤后2周就出现，并在4周时充分发展。这些改变见于多个附着点以及股骨和胫骨髁的内表面。在反应性附着点，向韧带中间物质的矿化附着导致矿化纤维软骨增厚。这些变化与ColX-RFP、Col1-CFP报告基因活性和碱性磷酸酶活性的增加有关。矿化附着在2周时也出现在内侧髁非关节区域的纤维软骨中，并在损伤后4周发展为骨赘。一个意外的观察结果是，在与活跃的附着性矿化相邻的未矿化纤维软骨细胞中，抗酒石酸酸性磷酸酶活性呈点状表达。
这些观察结果表明，纤维软骨在关节软骨降解之前就被激活。因此，纤维软骨的临床和组织学成像可能是疾病起始的更早指标，并且可能指示开始预防性治疗的更合适时间。
