Osteoclast depletion with clodronate liposomes delays fracture healing in mice.
Osteoclast depletion with clodronate liposomes delays fracture healing in mice.
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DOI：
10.1002/jor.23440
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发表时间：
2017-08
期刊：
影响因子：
--
通讯作者：
O'Connor JP
中科院分区：
文献类型：
--
作者：
Lin HN;O'Connor JP
破骨细胞在骨折骨痂内大量存在，也位于软骨-骨交界处。然而，破骨细胞在骨折愈合过程中的功能还没有很好的定义。抑制破骨细胞形成或吸收活性会损害骨痂重塑，但不会阻止骨痂形成。有趣的是，抗破骨细胞疗法对骨痂软骨分解成骨的影响不同。抑制破骨细胞形成或活力的治疗往往会损害愈伤组织软骨消退，而靶向抑制骨吸收的治疗通常不会影响愈伤组织软骨消退。在这里，我们测试了是否消耗破骨细胞的全身治疗与氯膦酸脂质体将同样损害骨痂软骨分辨率。ICR小鼠通过腹腔内注射氯膦酸盐负载脂质体或对照脂质体进行治疗，并进行闭合性股骨骨折。股骨在骨折后多次切除，并通过X线摄影、组织学和力学测试进行分析，以确定对愈合的影响。氯膦酸盐脂质体处理不能阻止愈伤组织的形成。然而，放射学评分表明，氯膦酸盐脂质体治疗损害愈合。氯膦酸盐脂质体治疗显着减少愈伤组织破骨细胞的人口和延迟解决愈伤组织软骨。与骨痂软骨的持续存在一致，扭转机械测试发现愈合28天后骨痂材料特性显著降低。结果支持破骨细胞在骨痂软骨分解成骨中的作用。破骨细胞的软骨分解作用是否仅限于在软骨-骨连接处吸收软骨，或通过另一种机制促进软骨-骨连接处的骨形成，可能类似于骨重建中的逆转过程，将需要进一步的实验。
Osteoclasts are abundant within the fracture callus and also localize at the chondro-osseous junction. However, osteoclast functions during fracture healing are not well defined. Inhibition of osteoclast formation or resorptive activity impairs callus remodeling but does not prevent callus formation. Interestingly though, anti-osteoclast therapies differentially affect resolution of callus cartilage into bone. Treatments that inhibit osteoclast formation or viability tend to impair callus cartilage resolution, while treatments that target inhibition of bone resorption generally do not affect callus cartilage resolution. Here we tested whether depletion of osteoclasts by systemic treatment with clodronate liposomes would similarly impair callus cartilage resolution. ICR mice were treated by intraperitoneal injections of clodronate-laden liposomes or control liposomes and subjected to closed femur fracture. Femurs were resected at multiple times after fracture and analyzed by radiography, histology, and mechanical testing to determine effects on healing. Clodronate liposome treatment did not prevent callus formation. However, radiographic scoring indicated that clodronate liposome treatment impaired healing. Clodronate liposome treatment significantly reduced callus osteoclast populations and delayed resolution of callus cartilage. Consistent with continued presence of callus cartilage, torsional mechanical testing found significant decreases in callus material properties after 28 days of healing. The results support a role for osteoclasts in the resolution of callus cartilage into bone. Whether the cartilage resolution role for osteoclasts is limited to simply resorbing cartilage at the chondro-osseous junction or in promoting bone formation at the chondro-osseous junction through another mechanism, perhaps similar to the reversal process in bone remodeling, will require further experimentation.
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DOI：
10.1038/bonekey.2014.56
发表时间：
2014
期刊：
BoneKEy reports
影响因子：
--
作者：
Delaisse, Jean-Marie
通讯作者：
Delaisse, Jean-Marie
影响因子：
6.2
作者：
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通讯作者：
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影响因子：
2.6
作者：
Maes, C;Carmeliet, P;Carmeliet, G
通讯作者：
Carmeliet, G
影响因子：
6.2
作者：
Alexander, Kylie A.;Chang, Ming K.;Pettit, Allison R.
通讯作者：
Pettit, Allison R.
影响因子：
3.7
作者：
Kamimura M;Mori Y;Sugahara-Tobinai A;Takai T;Itoi E
通讯作者：
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