Department of Rehabilitation, Shengjing Hospital of China Medical University, No.16, Puhe Street, Shenyang North New Area, Shenyang, 110134, Liaoning Province, China.
Department of Orthopaedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China.
BMC Musculoskelet Disord. 2021 Oct 12;22(1):870. doi: 10.1186/s12891-021-04735-2.
Matrix Gla (γ-carboxyglutamate) protein (MGP) is considered a strong inhibitor of ectopic calcification, and it has been associated with OA severity, although not conclusively. We utilized male Dunkin-Hartley (DH) guinea pigs to investigate the expression of MGP throughout aging and disease pathogenesis in a spontaneous model.
Twenty-five male DH guinea pigs were obtained and nurtured to several timepoints, and then randomly and equally divided by age into five subgroups (1-, 3-, 6-, 9-, and 12-months, with the 1-month group as the reference group). DH guinea pigs in each group were euthanized at the designated month-age and the left or right medial tibial plateaus cartilages were randomly excised. OA severity was described by modified Mankin Score (MMS) at microscopy (Safranin O/Fast Green stain). Proteomic evaluation using isobaric tags for relative and absolute quantification (iTRAQ) was performed to validate the age-related changes in the MGP profiles, and immunohistochemistry (IHC) methods were applied for semi-quantitative determination of MGP expression in articular cartilage.
The histopathologic findings validated the increasing severity of cartilage degeneration with age in the DH guinea pigs. The MMS showed significant, stepwise (every adjacent comparison P < 0.05) disease progression with month-age. The iTRAQ indicated that MGP levels increased significantly with advancing age (P < 0.05), as supported by the IHC result (P < 0.05).
Increased expression of MGP in male DH guinea pigs was present throughout aging and disease progression and may be link to increased OA severity. Further studies are needed to investigate and confirm the association between MGP levels and OA severity.
基质 Gla 蛋白（MGP）被认为是异位钙化的强抑制剂，尽管它与 OA 严重程度有关，但尚无定论。我们利用雄性 Dunkin-Hartley（DH）豚鼠在自发性模型中研究了整个老化过程和疾病发病机制中 MGP 的表达。
获得 25 只雄性 DH 豚鼠并进行饲养，然后按年龄随机分为五个亚组（1、3、6、9 和 12 个月，以 1 个月组为参考组）。每个亚组的 DH 豚鼠在指定的月龄时安乐死，并随机切除左或右内侧胫骨平台软骨。使用改良的曼金评分（MMS）在显微镜下（番红 O/快绿染色）描述 OA 严重程度。使用等重标记相对和绝对定量（iTRAQ）进行蛋白质组学评估，以验证 MGP 谱与年龄相关的变化，并应用免疫组织化学（IHC）方法半定量测定关节软骨中 MGP 的表达。
组织病理学发现验证了 DH 豚鼠软骨退行性变随年龄的增加而加重。MMS 显示出随着月龄的增加，疾病进展呈显著的递增（每相邻比较 P<0.05）。iTRAQ 表明 MGP 水平随年龄的增长而显著增加（P<0.05），IHC 结果也支持这一结果（P<0.05）。
雄性 DH 豚鼠中 MGP 的表达随着年龄的增长和疾病的进展而增加，可能与 OA 严重程度的增加有关。需要进一步研究以调查和确认 MGP 水平与 OA 严重程度之间的关联。
