甲状旁腺激素联合阿仑膦酸钠对大鼠骨质疏松性骨折骨痂血管形成的影响

目的探讨甲状旁腺激素联合阿仑膦酸钠对大鼠骨质疏松性骨折骨痂血管形成及骨折愈合的影响。方法 75只雌性SD大鼠随机分为5组:假手术组、去势组、甲状旁腺素组、阿仑膦酸钠组、联合用药组,每组15只,首先行双侧卵巢切除术,术后4周行右侧股骨干骨折髓内固定术,以构建大鼠骨质疏松性骨折动物模型。观察并评估骨折愈合,检测骨痂生物力学和骨密度(bone mineral density,BMD),检测血清血管内皮生长因子(vascular endothelial growth factor,VEGF)和骨形成发生蛋白-2(bone morphogenetic protein-2,BMP-2)浓度,观察骨痂形态结构,检测骨痂VEGF表达。结果去势组较假手术组骨折愈合评分、骨痂生物力学强度、骨痂BMD、血清BMP-2和VEGF浓度、骨痂VEGF蛋白表达、骨痂微血管数均显著降低(P0.05),甲状旁腺素组、阿仑膦酸钠组、联合用药组较去势组上述指标均升高,其中以联合用药组升高最显著(P0.05)。结论甲状旁腺激素联合阿仑膦酸钠通过介导VEGF,上调BMP-2表达,促进骨质疏松性骨折大鼠骨痂血管形成,增加骨密度,改善生物力学强度及骨组织形态学,加快骨折愈合。     

仙灵骨葆胶囊联合阿仑膦酸钠对骨质疏松骨折大鼠骨痂血管形成的影响

目的探讨仙灵骨葆胶囊联合阿仑膦酸钠对骨质疏松性骨折大鼠骨痂血管形成及VEGF、BMP-2表达的影响。方法50只雌性SD大鼠随机分为假手术组(SHAM组)、模型组(MODEL组)、仙灵骨葆组(XLGB组)、阿仑膦酸钠组(ALLSN组)、联合药物组(LHYW组),10只/组,构建骨质疏松性骨折大鼠模型,放射性X线观察评估骨折愈合,双能X线检测骨密度,Mirco-CT检测骨结构形态学参数,番红O固绿染色观察骨痂组织形态学,免疫组化检测骨痂VEGF和BMP-2蛋白表达。结果所有实验大鼠均进入结果分析。与SHAM组比较,MODEL组大鼠骨折愈合评分、骨密度、骨组织形态学参数、骨痂VEGF和BMP-2表达均显著降低(P0.05),与MODEL组比较,XLGB组、ALLSN组和LHYY组骨折愈合评分、骨密度、骨组织形态学参数、骨痂VEGF和BMP-2表达均显著升高(P0.05),尤以LHYY组最高。SHAM组骨小梁结构正常,几乎均为骨性骨痂。MODEL组骨小梁明显稀疏、断裂,未见明显骨性骨痂。XLGB组和ALLSN组骨小梁增多,排列稍紊乱,大部分为骨性骨痂。LHYW组骨小梁明显增多,排列密集整齐,大量骨性骨痂。结论仙灵骨葆胶囊联合阿仑膦酸钠可能通过介导提高骨质疏松性骨折大鼠骨生长因子VEGF和BMP-2表达,促进骨痂血管形成,加速骨痂形成,增加骨密度,改善骨结构形态,促进骨折愈合。     

去势延迟雄性小鼠骨折愈合

目的观察去势雄性小鼠骨折愈合的情况,探讨男性骨质疏松骨折愈合过程。方法40只7周龄C57BL/6J雄性小 鼠,其中8只作为基线组,32只随机分为对照组与去势组,小鼠去势后1周建立右股骨中段骨折模型。术后2周和4周,测量 血清睾酮浓度,骨折端骨密度（BMD)。骨折愈合情况通过显微CT和组织学切片显示。结果去势后小鼠血清睾酮浓度明显 下降;术后4周,与对照组相比,去势组BMD明显降低。三维重建图像显示去势组骨痂改建差于对照组。病理切片可见去势 组初级骨小梁少于对照组,骨痂重建差于对照组。结论去势延迟的骨折的愈合,表现在骨折区骨量减少以及骨改建延迟, 本研究为男性骨质疏松骨折的研究提供了动物模型。     

雷洛昔芬对OVX大鼠骨质疏松性骨折愈合的影响

目的 探讨骨质疏松性骨折愈合的特点以及雷诺昔芬对骨质疏松性骨折愈合的影响.方法 健康12 周龄雌性SD大鼠54只,随机分成假手术组(SHAM),卵巢切除+生理盐水组(OVX),卵巢切除+雷诺昔芬组(OVX+RAL),每组18只大鼠.卵巢切除术后8周,骨密度检测确认大鼠骨质疏松模型成功.选择开放性右侧股骨中段骨折模型,以克氏针行髓内固定股骨;骨折后8周,CR片记录大鼠骨痂的连续性以及骨折愈合情况,三点弯曲试验检测股骨的最大弯曲应力和最大弯曲载荷.取骨折术后4周和8周时骨痂,行HE染色,并记录骨小梁或小梁状骨所占体积比(BV/TV)表示.免疫组化染色检测骨痂中血管内皮生长因子(VEGF)表达.结果 CR摄片显示骨折后8周各组大鼠骨折连续性都较好,骨折对位对线好.大鼠骨折8周时最大弯曲应力和最大弯曲载荷,SHAM组和OVX+RAL组都明显优于OVX组,差异显著,有统计学意义.骨折4周时骨痂的HE染色中,OVX组原始小梁状骨中新生软骨细胞较多.OVX+RAL组和SHAM组8周时骨痂中BV/TV值明显高于OVX组.骨折4周时骨痂VEGF染色中,各组大鼠的骨痂内软骨细胞或骨细胞上存在一定量的VEGF表达,SHAM组和OVX+RAL组的细胞上VEGF表达量略高于OVX组;骨折8周时各组骨痂中的VEGF几乎无明显表达.结论 OVX大鼠骨痂成熟缓慢和早期骨痂内VEGF低表达,可能是骨折愈合能力下降的重要因素.雷诺昔芬可以促进骨痂成熟和早期骨痂中VEGF的表达,有利于OVX大鼠骨折愈合.     

海水浸泡开放性骨折伤愈合过程中组织病理学和血管内皮细胞生长因子(VEGF)表达

目的通过观察普通开放骨折、海水浸泡开放骨折愈合过程的组织学变化和骨痂中血管内皮细胞生长因子(VEGF)的表达,了解海水浸泡开放性骨折愈合过程VEGF的作用与机制。方法新西兰大白兔59只,随机分为普通开放骨折组(对照组)24只和海水浸泡开放骨折组(实验组)35只。造成桡骨横行1.5mm缺损完全开放骨折,普通开放骨折伤组旷置3h,海水浸泡开放骨折伤组海水浸泡伤口3h,之后依次缝合伤口。于第1、3、7、14、21、28、45天处死动物。观察海水浸泡开放骨折伤在骨折愈合中不同时间的病理过程。采用RT-PCR方法检测普通开放骨折、海水浸泡开放骨折不同阶段骨痂中的VEGF的表达及变化。结果海水浸泡开放骨折伤骨痂形成延迟,骨折后第28天,对照组断端间骨痂为骨性骨痂者8例,为软骨者4例,实验组断端间骨痂为骨性骨痂者6例,为软骨者14例。海水浸泡骨折伤愈合过程中新生骨痂的VEGF表达在骨折后逐渐升高,术后14d达到高峰,之后逐渐下降,但在28d时仍保持较高水平,与一般开放骨折愈合过程的VEGF表达无显著差异(P>0.05)。结论海水浸泡使骨折骨痂形成不良率增高,骨折愈合过程有延迟倾向;但骨折愈合过程中VEGF表达无明显变化。     

一氧化氮调节骨折愈合的实验研究

[目的] 探讨一氧化氮在骨折愈合中的可能作用。[方法] Wistar大鼠60只随机分为实验组和对照组。两组动物的饮用水分别含L-硝基-精氨酸甲基脂（L-NAME）和D-硝基-精氨酸甲基脂（D-NAME），建立股骨开放骨折模型，骨折后第3d、1、2和4周，取每组6只大鼠骨折处骨痂行HE染色观察。另6只大鼠于骨折后4周行骨痂的面积、骨密度和骨折的生物力学评价。[结果] 骨折后两组大鼠体重增加无差别。HE染色光镜下见骨折后不同时期L-NAME组骨折处骨痂生成少，骨痂塑形慢，未成熟细胞比例较对照组多（P〈0．05），加入L-NAME后使骨折愈合反应减小，实验组骨痂的大小、骨密度和愈合强度均明显低于对照组，有明显的统计学意义。[结论] 在骨折愈合过程中加入L-NAME会使骨折愈合减慢，一氧化氮可能促进骨折的愈合过程。     

重组人甲状旁腺激素1-34对骨质疏松性骨折愈合影响的实验研究

目的研究重组人甲状旁腺激素1-34（rhPTH1-34）片段对大鼠骨质疏松性骨折愈合的影响。方法选择6个月龄雌性SD大鼠80只，随机分为rhPTH1-34组、雌激素组、对照组（骨质疏松组）及假手术组，每组20只。前三组切除双侧卵巢，假手术组暴露卵巢而不切除，术后3个月行右侧股骨中段骨折内固定术。术后分别皮下注射rhPTH1-34、苯甲酸雌二醇及等量生理盐水，进行骨密度、X线片组织病理学和生物力学检测，观察骨折愈合情况。结果rhPTH1-34组骨折局部骨密度明显高于对照组，差异有统计学意义（P〈0．05）；rhPTH1-34组比同时期的对照组骨痂生成量多，愈合时间提前。结论rhPTH1-34能促进骨形成，增加骨量，加快骨痂形成，促进骨质疏松性骨折愈合，同时能提高骨生物力学特性和抗骨折能力。     

感觉/运动神经切断影响大鼠骨折愈合的实验研究

[目的]通过建立切断组成大鼠坐骨神经的不同成分、联合胫骨骨折的动物模型,来研究感觉/运动神经损伤对骨折愈合的影响,并进一步探讨周围神经系统对骨组织的生理作用。[方法]Wistar大鼠90只平均分为3组：对照组,运动神经（前根）切断组,感觉神经（后根）切断组,选择性切断一侧L4～6神经根。所有大鼠于神经根暴露侧/切断侧胫骨造成横行骨折,髓钉固定。30d后取大鼠双侧胫骨,测患侧胫骨近端骨密度、在影像学资料上测量患侧骨痂宽度及健侧胫骨相应位置的皮质宽度、取所有大鼠双侧胫骨行湿重称量、骨痂组织学切片观察、双侧胫骨行生物力学拉伸测试。所得结果均以患侧数据除以相应健侧数据得出一相对数,以相对数数据进行统计分析。[结果]患侧胫骨近端骨密度无显著差异（P〉0.05）;检测项目示神经切断组骨折处骨痂形成多,力学强度差,骨痂成熟度差（P〈0.05）,以感觉神经（后根）切断组尤甚（P〈0.05）[结论]感觉神经纤维对骨折愈合的影响较运动神经纤维显著;完整的神经支配是正常骨折愈合的必要条件。     

仙灵骨葆胶囊对骨质疏松性骨折大鼠骨生长因子及骨折愈合的影响

目的 探讨仙灵骨葆胶囊对骨质疏松性骨折大鼠骨生长因子BMP-2、IGF-1表达及骨折愈合的影响。方法 48只雌性SD大鼠随机分为：假手术组、模型组、雌二醇组、仙灵骨葆组，12只/组，采用“双侧卵巢切除术+右侧股骨干骨折髓内固定术”构建骨质疏松性骨折大鼠模型，评估骨折愈合情况，检测股骨骨痂BMD、股骨骨生物力学指标和血清骨代谢相关指标，检测骨痂BMP-2、IGF-1蛋白表达。结果 模型组较假手术组骨折愈合评分、股骨痂BMD、股骨骨生物力学指标（最大载荷、最大应力、最大位移）、骨痂BMP-2和IGF-I阳性表达均显著降低（P<0.05），雌二醇组、仙灵骨葆组较模型组骨折愈合评分、股骨痂BMD、股骨骨生物力学指标、骨痂BMP-2和IGF-I阳性表达均显著升高（P<0.05），均以仙灵骨葆组最高。模型组较假手术组血清骨代谢指标（BGP、PICP、TRACP-5b）均显著升高（P<0.05），雌二醇组、仙灵骨葆组较模型组血清骨代谢指标均显著降低（P<0.05），以仙灵骨葆组最低。结论 仙灵骨葆胶囊可能通过介导提高骨质疏松性骨折大鼠骨生长因子BMP-2和IGF-1表达，改善骨代谢，加速骨痂形成，增加骨密度，提高骨生物力学，促进骨折愈合。     

高压氧对小鼠胫骨骨折愈合过程中骨生物力学特性及胶原蛋白含量的影响

目的 探讨高压氧对小鼠胫骨骨折愈合过程中骨生物力学特性及胶原蛋白含量的影响.方法 采用简单随机抽样法将216 只昆明小鼠随机分为对照组（108 只）和高压氧组（108 只）,建立胫骨骨折模型.高压氧组予以高压氧治疗,对照组不予高压氧治疗.分别于骨折后1、2、3、4 周取材,取材前通过行为学评分和斜板实验评价两组小鼠的行为学特征,观察取材后胫骨的一般生物学特征,检测胫骨标本的抗扭力和抗折力,测定胫骨骨痂组织的胶原蛋白含量,同时采用改良Masson 染色对骨痂组织中的胶原蛋白进行组织学观察.结果 与对照组相比,高压氧组小鼠骨折后1、2 周行为学评分降低;2、3、4 周斜板实验坡度升高（P ＜0.05）.骨折后1周高压氧组小鼠右侧胫骨宽度（骨痂处）、胫骨抗折力均大于对照组,两组比较,差异有统计学意义（P ＜0.05）;骨折后2 周高压氧组小鼠右侧胫骨抗扭力高于对照组,骨折后1、2、3 周右侧与左侧胫骨抗扭力比值以及两侧胫骨抗折力比值均高于对照组,两组比较,差异有统计学意义（P ＜0.05）;高压氧组小鼠骨折后1、2、3、4 周骨痂胶原纤维含量高于对照组（P ＜0.05）,且高压氧组改良Masson染色出现较多的蓝色反应.结论 在小鼠胫骨骨折的愈合过程中,高压氧治疗提高了骨痂组织中胶原蛋白的含量,增强了骨的生物力学性能,对骨折愈合起到促进作用.     

Bone loss and impaired fracture healing in spinal cord injured mice

Summary

Spinal cord injury (SCI) results in impaired fracture healing in mice while leading to significant bone loss. Poor fracture healing following SCI is consistent with significant bone loss.

Introduction

SCI leads to significant bone loss in sublesional limbs, but there is few data concerning the relationship between fracture healing and bone loss following SCI. This study was undertaken to investigate the effect of SCI on fracture healing using a mouse femur fracture model.

Methods

One hundred twenty male C57BL/6J mice were randomly divided into SCI and control groups (n?=?60, respectively). A femoral shaft fracture was generated and fixed with intramedullary pins 3?weeks after SCI. Fracture healing was evaluated by micro-computed tomography (micro-CT) for callus formation and mineralization and neovascularization, and bone mineral density (BMD) was measured by DXA at 1, 2, and 4?weeks after fracture. Serum vascular endothelial growth factor (VEGF), osteocalcin, and alkaline phosphatase (ALP) were assessed using ELISA at each time point. Biomechanical testing was performed at 2 and 4?weeks.

Results

BMD in SCI mice was significantly lower compared to control mice at each time point, with callus volume and all vessel parameters reduced as measured by micro-CT. Ultimate stress of the femora was significantly lower in SCI mice than in control mice at 2 and 4?weeks after fracture, whereas Young's modulus between the SCI and control mice turned to be significantly different at 4?weeks. Serum VEGF was lower in SCI mice than in the control group at 2 and 4?weeks, whereas serum osteocalcin and ALP were lower in SCI mice than in control ones at each time point.

Conclusion

Significant bone loss and fracture healing impairment was noted in SCI mice. Decreased angiogenesis is consistent with the changes of microarchitecture and biomechanical properties during fracture healing.     

血管内皮生长因子在骨折伴颅脑损伤患者血清中的表达

目的探讨骨折伴颅脑损伤患者血清中血管内皮生长因子(VEGF)与骨折愈合的关系。方法收集我院2008年9月至2010年9月期间收治的骨折患者40例,分为骨折伴颅脑损伤组及单纯骨折组,每组各20例。采用双抗体夹心酶联免疫吸附试验(ELISA)测定所有患者血清中VEGF水平,并摄X线片观察骨痂出现及骨折愈合情况,分析VEGF水平变化及骨折愈合过程。结果骨折伴颅脑损伤患者血清中VEGF含量在7d左右出现高峰期(519±44ng/ml),维持较高水平至42d,以后逐渐下降;单纯骨折患者血清中VEGF含量在14d左右为高峰期(438±28ng/ml),28d左右开始逐渐下降。骨折伴颅脑损伤患者骨痂形成时间(8d±0.3d)明显早于单纯骨折患者(18d±0.1d),P<0.01;骨折伴颅腑损伤患者骨折愈合时间(42d±0.4d)明显早于单纯骨折患者(84d±0.2d),P<0.01。结论骨折伴颅脑损伤患者血清中VEGF含量明显高于单纯骨折患者,骨痂形成及骨折愈合时间均比单纯骨折患者所需时间短。颅脑损伤患者VEGF升高可能是骨折愈合加快的原因之一。     

Do serological tissue turnover markers represent callus formation during fracture healing?

Serological parameters of bone and fibrous tissue turnover were demonstrated to monitor the course of fracture healing. The aim of this study was to evaluate the correlation between the serological parameter levels during fracture healing and callus development in a standardised ovine model of fracture healing. Two years old female sheep received a standardised 3 mm tibial bone defect stabilised by an external fixator. The serological levels of the C-terminal propeptide of procollagen type I (PICP), bone specific alkaline phosphatase (bALP), total alkaline phosphatase (tALP), osteocalcin, tartrate-resistant acid phosphatase (TRAP), calcium, phosphate and the N-terminal peptide of procollagen type III (PIIINP) were observed over a 9-week healing period. The course of fracture healing was monitored radiographically, and the callus composition was evaluated histologically at 2, 3, 6 and 9 weeks post-surgery. The serological results were compared with an untreated control group. Additionally, the maximum values during healing were compared with juvenile values to gauge the level of the serological response. The histological and radiographical results demonstrated callus formation without complications. All serological parameters showed broad inter-individual variations, and the response to the standardised fracture scenario was strongly individual. Maximum values during fracture healing did not reach the juvenile levels. The fractured as well as the control animals showed significant changes in the parameter levels. No correlations were observed between the histological course of healing and the course of bone formation markers whilst the TRAP level was reduced during bony callus formation. The PIIINP level increased when the amount of soft callus tissue decreased during healing. The observed bone formation markers were not suitable as general markers to detect the course of fracture healing, whilst PIIINP was able to reflect soft callus degradation.     

Delayed Fracture Healing in Aged Senescence-Accelerated P6 Mice

ABSTRACT

Background: Osteoporosis is characterized by poor bone quality. However, it is still controversially discussed whether osteoporosis compromises fracture healing. Herein, we studied whether the course of healing of a femur fracture is affected by osteoporosis or age. Methods: Using the senescence-accelerated osteoporotic mouse, strain P6 (SAMP6), and a closed femur fracture model, we studied the process of fracture healing in 5- and 10-month-old animals, including biomechanical, histomorphometric, and protein biochemical analysis. Results: In five-month-old osteoporotic SAMP6 mice, bending stiffness, callus size, and callus tissue distribution as well as the concentrations of the bone formation marker osteocalcin and the bone resorption markers tartrate-resistant acid phosphatase form 5b (TRAP) and deoxypyridinoline (DPD) did not differ from that of non-osteoporotic, senescence-resistant, strain 1 (SAMR1) controls. In contrast, femur fractures in 10-month-old SAMP6 mice showed a significantly reduced bending stiffness and an increased callus size compared to fractures in age-matched SAMR1 controls. This indicates a delayed fracture healing in advanced age SAMP6 mice. The delay of fracture healing was associated with higher concentrations of TRAP and DPD. Significant differences in osteocalcin concentrations were not found between SAMP6 animals and SAMR1 controls. Conclusion: In conclusion, the present study indicates that fracture healing in osteoporotic SAMP6 mice is not affected in five-month-old animals, but delayed in animals with an age of 10 months. This is most probably due to the increased osteoclast activity in advanced age SAMP6 animals.     

Systemic leptin administration alters callus VEGF levels and enhances bone fracture healing in wildtype and ob/ob mice

IntroductionLeptinʼs role in bone formation has been reported, however, its mechanism of affecting bone metabolism is remaining unclear. In this study, we aimed to test whether leptin has a positive effect on fracture healing through the possible mechanism of increasing vascular endothelial growth factor (VEGF) expression in callus tissue.MethodsStandardized femur fractures were created in leptin-deficient ob/ob and wildtype C57BL/6J mice, and recombinant mouse leptin or its vehicle (physiological saline) was administered intraperitoneally during the study. Body weight, radiological, histologic and immunoblotting analyses were performed at different stages of fracture healing.Key findingsThe results showed that leptin treatment led to lower rate of body weight change in both mice genotypes. Radiological and histological analyses showed that the experimental groups had better fracture healing at 14, 21 and 28 days compared to the control groups. Leptin-treated groups had significantly higher VEGF expression in callus compared with the control groups at 2 and 3 weeks post-fracture except normal mice at 2 weeks, and leptin-deficient mice had higher VEGF levels in calluses than normal mice at the same timepoint.ConclusionLow-dose systemically-administered leptin has a positive effect on promoting fracture healing during the latter stages in a clinically-relevant mouse bone fracture model, and increase callus VEGF levels.     

动态压应力对骨折愈合时骨痂矿化过程的影响

[目的]探讨持续动态压应力对实验性骨折愈合时骨折间隙内骨痂矿化过程的影响。[方法]新西兰兔肱骨干横断截骨，试验组以天鹅记忆接骨器内固定，对照组以4孔加压钢板内固定。分别于术后第2、3、4、8、12周时，在骨折间隙取材，并于术后1、2、3、4、8、12周时抽取血标本，经比色法测定骨痂钙、磷元素含量及血中骨特异性碱性磷酸酶的活性。[结果]试验组和对照组骨折间隙内骨痂钙、磷元素的含量均逐渐升高；血中骨特异性碱性磷酸酶的活性分别于术后4、8周升至峰值，随后缓慢下降。术后3～4周时试验组以上指标均明显高于对照组。[结论]天鹅记忆接骨器产生的持续动态压应力可能促进了骨痂的矿化和软骨内成骨。     

Urokinase plasminogen activator gene deficiency inhibits fracture cartilage remodeling

Urokinase plasminogen activator (uPA) regulates a proteolytic cascade of extracellular matrix degradation that functions in tissue development and tissue repair. The development and remodeling of the skeletal extracellular matrix during wound healing suggests that uPA might regulate bone development and repair. To determine whether uPA functions regulate bone development and repair, we examined the basal skeletal phenotype and endochondral bone fracture repair in uPA-deficient mice. The skeletal phenotype of uPA knockout mice was compared with that of control mice under basal conditions by dual-energy X-ray absorptiometry and micro-CT analysis, and during femur fracture repair by micro-CT and histological examination of the fracture callus. No effects of uPA gene deficiency were observed in the basal skeletal phenotype of the whole body or the femur. However, uPA gene deficiency resulted in increased fracture callus cartilage abundance during femur fracture repair at 14 days healing. The increase in cartilage corresponded to reduced tartrate-resistant acid phosphatase (TRAP) staining for osteoclasts in the uPA knockout fracture callus at this time, consistent with impaired osteoclast-mediated remodeling of the fracture cartilage. CD31 staining was reduced in the knockout fracture tissues at this time, suggesting that angiogenesis was also reduced. Osteoclasts also colocalized with CD31 expression in the endothelial cells of the fracture tissues during callus remodeling. These results indicate that uPA promotes remodeling of the fracture cartilage by osteoclasts that are associated with angiogenesis and suggest that uPA promotes angiogenesis and remodeling of the fracture cartilage at this time of bone fracture repair.     

Anti-DKK1 antibody promotes bone fracture healing through activation of β-catenin signaling

In this study we investigated if Wnt/β-catenin signaling in mesenchymal progenitor cells plays a role in bone fracture repair and if DKK1-Ab promotes fracture healing through activation of β-catenin signaling. Unilateral open transverse tibial fractures were created in CD1 mice and in β-catenin^Prx1ER conditional knockout (KO) and Cre-negative control mice (C57BL/6 background). Bone fracture callus tissues were collected and analyzed by radiography, micro-CT (μCT), histology, biomechanical testing and gene expression analysis. The results demonstrated that treatment with DKK1-Ab promoted bone callus formation and increased mechanical strength during the fracture healing process in CD1 mice. DKK1-Ab enhanced fracture repair by activation of endochondral ossification. The normal rate of bone repair was delayed when the β-catenin gene was conditionally deleted in mesenchymal progenitor cells during the early stages of fracture healing. DKK1-Ab appeared to act through β-catenin signaling to enhance bone repair since the beneficial effect of DKK1-Ab was abrogated in β-catenin^Prx1ER conditional KO mice. Further understanding of the signaling mechanism of DKK1-Ab in bone formation and bone regeneration may facilitate the clinical translation of this anabolic agent into therapeutic intervention.