Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
Key Laboratory of Bone and Cartilage Regeneration Medicine, Southern Medical University, Guangzhou, Guangdong 510515, China.
Int J Med Sci. 2021 Oct 22;18(16):3808-3820. doi: 10.7150/ijms.63401. eCollection 2021.
Substantial evidence shows that crosstalk between cartilage and subchondral bone may play an important role in cartilage repair. Animal models have shown that hydroxyapatite-grafted-chitosan implant (HA-g-CS) and moderate-intensity exercise promote regeneration of osteochondral defects. However, no studies have demonstrated that these two factors may have a synergistic activity to facilitate subchondral bone remodeling in mice, thus supporting bone-cartilage repair. This study was to clarify whether HA-g-CS and moderate-intensity exercise might have a synergistic effect on facilitating (1) regeneration of osteochondral defects and (2) subchondral bone remodeling in a mouse model of osteochondral defects. Mouse models of osteochondral defects were created and divided into four groups. BC Group was subjected to no treatment, HC Group to HA-g-CS implantation into osteochondral defects, ME group to moderate-intensity treadmill running exercise, and HC+ME group to both HA-g-CS implantation and moderate-intensity exercise until sacrifice. Extent of subchondral bone remodeling at the injury site and subsequent cartilage repair were assessed at 4 weeks after surgery. Compared with BC group, HC, ME and HC+ME groups showed more cartilage repair and thicker articular cartilage layers and HC+ME group acquired the best results. The extent of cartilage repair was correlated positively to bone formation activity at the injured site as verified by microCT and correlation analysis. Histology and immunofluorescence staining confirmed that bone remodeling activity was increased in HC and ME groups, and especially in HC+ME group. This bone formation process was accompanied by an increase in osteogenesis and chondrogenesis factors at the injury site which promoted cartilage repair. In a mouse model of osteochondral repair, HA-g-CS implant and moderate-intensity exercise may have a synergistic effect on improving osteochondral repair potentially through promotion of subchondral bone remodeling and generation of osteogenesis and chondrogenesis factors. Combination of HA-g-CS implantation and moderate-intensity exercise may be considered potentially in clinic to promote osteochondral defect repair. Also, cartilage and subchondral bone forms a functional unit in an articular joint and subchondral bone may regulate cartilage repair by secreting growth factors in its remodeling process. However, a deeper insight into the exact role of HA-g-CS implantation and moderate-intensity exercise in promoting osteochondral repair in other animal models should be explored before they can be applied in clinic in the future.
大量证据表明，软骨和软骨下骨之间的串扰可能在软骨修复中发挥重要作用。动物模型表明，羟基磷灰石接枝壳聚糖植入物（HA-g-CS）和中等强度运动促进了骨软骨缺损的再生。然而，尚无研究表明这两个因素可能具有协同作用，从而促进小鼠软骨下骨重塑，从而支持骨-软骨修复。本研究旨在阐明 HA-g-CS 和中等强度运动是否可能对促进（1）骨软骨缺损的再生和（2）骨软骨缺损小鼠模型中的软骨下骨重塑具有协同作用。创建了骨软骨缺损的小鼠模型，并将其分为四组。BC 组未进行任何治疗，HC 组将 HA-g-CS 植入骨软骨缺损，ME 组进行中等强度跑步机运动，HC+ME 组进行 HA-g-CS 植入和中等强度运动，直至处死。手术后 4 周评估损伤部位软骨下骨重塑的程度和随后的软骨修复情况。与 BC 组相比，HC、ME 和 HC+ME 组显示出更多的软骨修复和更厚的关节软骨层，而 HC+ME 组的效果最佳。软骨修复的程度与受伤部位的骨形成活性呈正相关，这一点通过 microCT 和相关分析得到了验证。组织学和免疫荧光染色证实，HC 和 ME 组骨重塑活性增加，尤其是在 HC+ME 组。这种骨形成过程伴随着损伤部位成骨和成软骨因子的增加，从而促进了软骨修复。在骨软骨修复的小鼠模型中，HA-g-CS 植入物和中等强度运动可能通过促进软骨下骨重塑和产生成骨和成软骨因子，对改善骨软骨修复具有协同作用。HA-g-CS 植入物和中等强度运动的联合应用可能在临床上被考虑用于促进骨软骨缺损修复。此外，软骨和软骨下骨在关节中形成一个功能单元，软骨下骨在其重塑过程中通过分泌生长因子来调节软骨修复。然而，在将来将其应用于临床之前，应该在其他动物模型中更深入地探讨 HA-g-CS 植入物和中等强度运动在促进骨软骨修复中的确切作用。
