Pensak Michael, Hong Seung-Hyun, Dukas Alex, Bayron Jennifer, Tinsley Brian, Jain Ashish, Tang Amy, Rowe David, Lieberman Jay R
University of Connecticut Health Center, Farmington, Connecticut.
University of Connecticut, Storrs, Connecticut.
J Orthop Res. 2015 Aug;33(8):1242-9. doi: 10.1002/jor.22896. Epub 2015 May 14.
Orthopaedic surgeons continue to search for cost-effective bone graft substitutes to enhance bone repair. Teriparatide (PTH 1-34) and demineralized bone matrix (DBM) have been used in patients to promote bone healing. We evaluated the efficacy of PTH and DBM in healing a critical sized femoral defect in three lineage-specific transgenic mice expressing Col3.6GFPtopaz (pre-osteoblastic marker), Col2.3GFPemerald (osteoblastic marker) and α-SMA-Cherry (pericyte/myofibroblast marker). Mid-diaphyseal defects measuring 2 mm in length were created in the central 1/3 of mice femora using a circular saw and stabilized with an alveolar distractor device and cerclage wires. Three groups were evaluated: Group I, PTH 30 μg/kg injection daily, Group II, PTH 30 μg/kg injection daily + DBM, and Group III, DBM + 30μL saline injection. PTH was given for 28 days or until the time of sacrifice. Animals were sacrificed at 7, 14, 28, and 56 days. Radiographs at the time of sacrifice were evaluated using a 5-point scaled scoring system. Radiographs showed a lack of healing across all treatment groups at all time points: Group I, 1.57 +/- 0.68; Group II, 3.00 +/- 1.29; and Group III, 2.90 +/- 1.03. Bone formation in the defect as measured by radiographic healing score was significantly better at 56 days in Groups II (p = 0.01) and III (p < 0.01) compared to Group I. Across all treatment groups and time points the defects were largely absent of osteoprogenitor cells based on gross observation of frozen histology and quantitation of cellular based histomorphometric parameters. Quantitation of frozen histologic slides showed a limited osteoprogenitor response to PTH and DBM. Our results suggest that the anabolic agent teriparatide is unable to induce healing in a critical sized mouse femoral defect when given alone or in combination with the DBM preparation we used as a local bone graft substitute.
骨科医生一直在寻找具有成本效益的骨移植替代物来促进骨修复。特立帕肽（甲状旁腺激素1-34）和脱矿骨基质（DBM）已用于患者以促进骨愈合。我们评估了甲状旁腺激素和脱矿骨基质在三种表达Col3.6GFPtopaz（前成骨细胞标志物）、Col2.3GFPemerald（成骨细胞标志物）和α-SMA-Cherry（周细胞/肌成纤维细胞标志物）的谱系特异性转基因小鼠中愈合临界尺寸股骨缺损的疗效。使用圆锯在小鼠股骨中部1/3处制造长度为2毫米的中骨干缺损，并用牙槽撑开器装置和环扎钢丝固定。评估了三组：第一组，每天注射30μg/kg甲状旁腺激素；第二组，每天注射30μg/kg甲状旁腺激素 + DBM；第三组，DBM + 注射30μL生理盐水。给予甲状旁腺激素28天或直至处死。在第7、14、28和56天处死动物。在处死时使用5分制评分系统评估X线片。X线片显示在所有时间点所有治疗组均缺乏愈合：第一组，1.57 ± 0.68；第二组，3.00 ± 1.29；第三组，2.90 ± 1.03。与第一组相比，在第56天时，通过X线愈合评分测量的缺损处骨形成在第二组（p = 0.01）和第三组（p < 0.01）中明显更好。基于对冷冻组织学的大体观察和基于细胞的组织形态计量学参数的定量，在所有治疗组和时间点，缺损处基本上没有骨祖细胞。对冷冻组织学切片的定量显示骨祖细胞对甲状旁腺激素和脱矿骨基质的反应有限。我们的结果表明，合成代谢剂特立帕肽单独使用或与我们用作局部骨移植替代物的脱矿骨基质制剂联合使用时，无法在临界尺寸的小鼠股骨缺损中诱导愈合。
