Orthopaedic Research & Biotechnology Unit, The Children's Hospital at Westmead, Sydney, Australia.
BMC Musculoskelet Disord. 2011 Dec 22;12:288. doi: 10.1186/1471-2474-12-288.
Bone repair is dependent on the presence of osteocompetent progenitors that are able to differentiate and generate new bone. Muscle is found in close association with orthopaedic injury, however its capacity to make a cellular contribution to bone repair remains ambiguous. We hypothesized that myogenic cells of the MyoD-lineage are able to contribute to bone repair.
We employed a MyoD-Cre+:Z/AP+ conditional reporter mouse in which all cells of the MyoD-lineage are permanently labeled with a human alkaline phosphatase (hAP) reporter. We tracked the contribution of MyoD-lineage cells in mouse models of tibial bone healing.
In the absence of musculoskeletal trauma, MyoD-expressing cells are limited to skeletal muscle and the presence of reporter-positive cells in non-muscle tissues is negligible. In a closed tibial fracture model, there was no significant contribution of hAP+ cells to the healing callus. In contrast, open tibial fractures featuring periosteal stripping and muscle fenestration had up to 50% of hAP+ cells detected in the open fracture callus. At early stages of repair, many hAP+ cells exhibited a chondrocyte morphology, with lesser numbers of osteoblast-like hAP+ cells present at the later stages. Serial sections stained for hAP and type II and type I collagen showed that MyoD-lineage cells were surrounded by cartilaginous or bony matrix, suggestive of a functional role in the repair process. To exclude the prospect that osteoprogenitors spontaneously express MyoD during bone repair, we created a metaphyseal drill hole defect in the tibia. No hAP+ staining was observed in this model suggesting that the expression of MyoD is not a normal event for endogenous osteoprogenitors.
These data document for the first time that muscle cells can play a significant secondary role in bone repair and this knowledge may lead to important translational applications in orthopaedic surgery. Please see related article: http://www.biomedcentral.com/1741-7015/9/136.
骨修复依赖于具有分化和生成新骨能力的成骨祖细胞。肌肉与骨科损伤密切相关，但其对骨修复的细胞贡献仍存在争议。我们假设 MyoD 谱系的肌源性细胞能够参与骨修复。
我们使用了一种 MyoD-Cre+:Z/AP+条件报告小鼠，其中 MyoD 谱系的所有细胞都永久标记有人类碱性磷酸酶（hAP）报告基因。我们在小鼠胫骨愈合模型中追踪了 MyoD 谱系细胞的贡献。
在没有肌肉骨骼创伤的情况下，MyoD 表达细胞仅限于骨骼肌，非肌肉组织中报告阳性细胞的存在可以忽略不计。在闭合性胫骨骨折模型中，hAP+细胞对愈合骨痂没有显著贡献。相比之下，带有骨膜剥离和肌肉开窗的开放性胫骨骨折中，开放性骨折骨痂中检测到多达 50%的 hAP+细胞。在修复的早期阶段，许多 hAP+细胞表现出软骨细胞的形态，而在后期阶段则存在较少数量的成骨细胞样 hAP+细胞。对 hAP 和 II 型和 I 型胶原进行连续切片染色显示，MyoD 谱系细胞被软骨或骨基质包围，提示其在修复过程中具有功能作用。为了排除在骨修复过程中，成骨前体细胞自发表达 MyoD 的可能性，我们在胫骨中创建了一个干骺端钻孔缺陷模型。在该模型中未观察到 hAP+染色，这表明 MyoD 的表达不是内源性成骨前体细胞的正常事件。
这些数据首次证明肌肉细胞可以在骨修复中发挥重要的次要作用，这一知识可能会为骨科手术带来重要的转化应用。请参阅相关文章：http://www.biomedcentral.com/1741-7015/9/136。
