整体填充和颗粒填充β-TCP植骨材料对修复腔隙性骨缺损的影响

目的:探讨不同植骨方法对于β-TCP(β-Tricalcium phosphate,β-TCP)植骨材料修复兔股骨腔隙性骨缺损的效果.方法:24只成年家兔,被随机分为整体填充组(12例)和颗粒填充组(12例).以膝关节外侧切口入路,在双侧股骨髁部制备6mm(直径)×10mm(深度)骨缺损,按照事先随机分组结果,分别进行整体填充植骨和颗粒填充植骨.分别于术后3至6周处死动物,取材标本进行生物力学分析,Micro-CT检测和组织学观察.结果:3周时,整体填充组的最大抗压强度明显优于颗粒填充组(P＜0.05),而Micro-CT检测发现新生骨密度(tissue mineral density,TMD)和新生骨体积百分比(bone volume fraction,BV/TV)在两组间均无明显差异,组织学在两组均表现为少量新骨形成;6周时,两组之间的最大抗压强度无明显差异,而Micro-CT检测显示颗粒填充组的TMD和BV/TV均优于整体填充组(P＜0.05),组织学上颗粒填充组较整体填充组可见较多的新骨形成.结论:整体填充组提供了更好的生物学强度,颗粒填充组更有利于诱导新骨形成,二者各有优点.     

骨诱导无机材料BAM 修复牙种植体周围骨缺损的实验研究

目的:评价骨诱导磷酸钙生物陶瓷(BAMOICPC)与可吸收胶原膜(BME-10X医用胶原膜)在牙种植体周围骨缺损中的修复能力。方法:在兔股骨上植入羟基磷灰石涂层BLB种植体,然后在其侧壁制造高4 mm、宽3 mm、深2 mm的骨缺损。对照组为单纯侧壁骨缺损,实验A组骨缺损区仅覆盖BME-10X膜,B组骨缺损区植入BAMOICPC,C组骨缺损区植入BAMOICPC并加盖BME-10X膜。于术后6个月取带种植体的骨段,通过HE染色和扫描电镜(SEM)分析。结果:对照组骨缺损区种植体表面见纤维包裹,实验A组骨缺损边界区少许骨质移行覆盖,实验B组下半部分缺损区新生骨覆盖。C组新生骨完全覆盖骨缺损区,且较B组硬度高,扫描电镜见与种植体结合更紧密。组织学观察B、C两实验组新生骨均可见比较成熟的哈弗氏管系统。结论:骨诱导磷酸钙生物陶瓷BAMOICPC是一种较理想的骨替代材料,联合运用胶原膜修复种植体周骨缺损效果佳。     

胶原蛋白/BMP复合材料的制备和成骨性能研究

以胶原膜(含87.5 mg I型胶原蛋白)为载体, 复合3.5 mg rhBMP-2(人基因重组骨形成蛋白-2), 制备胶原蛋白/BMP复合材料。复合材料首先在兔背阔肌中埋置, 预构新生骨组织, 并采用ALP染色、Von Kossa染色和HE染色等观察复合材料的成骨过程和组织形态。然后将形成的新骨组织游离移植修复自体下颌骨体部洞穿性缺损; 并设以胶原为载体的rhBMP-2复合骨修复材料直接修复为对照组, 骨缺损不修复组为空白组。采用X线、抗压强度、硬组织切片、四环素荧光染色、骨形态计量检查, 观察复合材料修复骨缺损的质量和效果。结果表明, 胶原蛋白/BMP复合材料在兔背阔肌中4～6周成骨, 胶原材料于3～5周降解; 成骨过程为是以软骨成骨为主的方式, 新骨形态为编织骨, 可见明显的微血管分布; 游离移植修复自体下颌骨缺损, 6周缺损区为骨性愈合, 与对照组在抗压强度(P = 0.041)、新骨量(P = 0.034)均有显著性差异。胶原蛋白/BMP复合材料在骨骼肌中形成的新生骨组织可作为供骨修复一定范围的骨缺损。     

胶原蛋白/BMP复合材料的制备和成骨性能研究

以胶原膜(含87.5 mg I型胶原蛋白)为载体, 复合3.5 mg rhBMP-2(人基因重组骨形成蛋白-2), 制备胶原蛋白/BMP复合材料。复合材料首先在兔背阔肌中埋置, 预构新生骨组织, 并采用ALP染色、Von Kossa染色和HE染色等观察复合材料的成骨过程和组织形态。然后将形成的新骨组织游离移植修复自体下颌骨体部洞穿性缺损; 并设以胶原为载体的rhBMP-2复合骨修复材料直接修复为对照组, 骨缺损不修复组为空白组。采用X线、抗压强度、硬组织切片、四环素荧光染色、骨形态计量检查, 观察复合材料修复骨缺损的质量和效果。结果表明, 胶原蛋白/BMP复合材料在兔背阔肌中4～6周成骨, 胶原材料于3～5周降解; 成骨过程为是以软骨成骨为主的方式, 新骨形态为编织骨, 可见明显的微血管分布; 游离移植修复自体下颌骨缺损, 6周缺损区为骨性愈合, 与对照组在抗压强度(P = 0.041)、新骨量(P = 0.034)均有显著性差异。胶原蛋白/BMP复合材料在骨骼肌中形成的新生骨组织可作为供骨修复一定范围的骨缺损。     

表面改性双相陶瓷复合自体骨髓干细胞修复兔骨缺损的实验研究

目的:应用自体骨髓基质干细胞(Bone Marrow Stromal Cells,BMSCs)复合经低晶态羟基磷灰石(Low Crystalline Hydroxyap- atite,LcHA)涂层的双相陶瓷(Biphasic Calcium Phosphate,BCP)构建的组织工程化骨(LcBCP)修复兔桡骨节段性缺损。方法:体外分离培养、诱导扩增兔BMSCs,取第三代细胞复合LcBCP(实验组)后修复15只兔左侧桡骨15mm缺损;右侧桡骨缺损处植入复合BMSCs的BCP(对照组),于植入后4、8和12周处死动物,通过大体形态、组织学、影像学和扫描电镜检测骨缺损修复效果。结果:BMSCs-LcBCP复合物生长良好,随时间延长,X线显示实验组连接处骨痂形成,对照组连接处始终愈合稍差,12周大体观察实验组骨修复良好,髓腔再通;组织学显示板层骨形成,连接处骨性愈合,实验对照组连接处虽然也为骨性愈合,但尚有较多编织骨形成。结论:自体BMSCs复合LcBCP形成的组织工程化骨可修复兔桡骨节段性缺损,低晶态羟基磷灰石涂层能够增强双相陶瓷的早期成骨。     

绵羊羊膜上皮细胞治疗兔桡骨缺损模型的研究

为了确定绵羊羊膜上皮细胞在体内向骨组织的分化能力,实验在分离培养绵羊羊膜上皮细胞并对其进行干细胞特性的鉴定的基础上,制作新西兰大白兔桡骨13mm骨缺损模型,随机分组对其进行注射绵羊羊膜上皮细胞实验。高剂量组:移植细胞5×107个;低剂量组:移植细胞5×106个;对照组:生理盐水。细胞移植后2、4、8周拍摄X光片观察骨缺损部位的缺损修复情况;相应时段取骨缺损部位新生骨进行组织学观察:分析骨小梁生成数量和骨的改建时期。实验结果显示,高剂量实验组在移入细胞第8周,骨缺损完全修复,且同期高剂量组新骨生成的数量和质量明显高于低剂量组,低剂量组优于对照组。由此可见,绵羊羊膜上皮细胞不仅可以在不同种动物间进行移植,而且对骨缺损有良好的修复能力。     

应用3D适形打印制备网状复合体对兔颅骨缺损的修复作用及安全性研究

目的:探讨采用3D适形打印技术制备的羟基磷灰石/聚乳酸网状复合体在兔颅骨缺损中的修复作用及安全性。方法:以24只新西兰兔为研究对象,以羟基磷灰石/聚乳酸为材料,采用3D适形打印技术制备网状复合体,于兔颅骨顶部制成两个颅骨全层缺损,分别为孔A(左)和孔B(右),孔A(阳性对照组)以自体颅骨为修复材料,孔B(实验组)以复合体为修复材料,观察缺损修复区域的形态学、影像学(X线及CT扫描)及组织学检查结果。结果:植入后24周时,形态学显示:阳性对照组可见致密的骨组织修复,与缺损边缘界限不清,实验组中支架孔隙内纤维组织由新生骨质取代,且新生骨成熟度较提高,材料表面有部分吸收。CT扫描观察显示:冠状面上,阳性对照组缺损修复区域与周围正常骨组织融合为一体,实验组修复材料与缺损边缘融合紧密,与周围正常骨组织结合良好,部分边缘结合不连贯。组织学观察显示:实验组材料部分降解,材料间隔可见新生骨小梁。研究中无实验动物死亡,皮肤切口处缝合良好,无皮下积液,无移植物脱出、红肿感染等情况出现。结论:以3D适形打印技术制备的羟基磷灰石/聚乳酸复合体对兔颅骨缺损有较好的修复作用,能促进缺损区域新骨的形成和生长,且安全性较高。     

生长激素-海藻酸钠-壳聚糖微胶囊促进骨折愈合的组织学研究

目的:观察生长激素-海藻酸钠-壳聚糖微胶囊促进兔挠骨骨折愈合的作用。方法:实验将新西兰兔80只,在制备新西兰兔右桡骨中段3mm骨缺损模型的基础上,随机分成四组:口服生长激素-海藻酸钠-壳聚糖微胶囊组、皮下注射生长激素组、口服空微胶囊组和生理盐水对照组。实验组口服生长激素-海藻酸钠-壳聚糖微胶囊和皮下注射生长激素,对照组口服空微胶囊。并于术后9、17、30、42d定期HE染色和地衣红染色观察各组的骨折愈合情况。结果:本实验HE染色结果表明,由于在骨缺损部位成纤维细胞产生的大量胶原纤维为基质,形成透明软骨及成骨细胞,骨小梁生长的基础,连接骨痂形成和骨髓腔贯通。而观察到生长激素微胶囊组各期提前生长及改建提前的形态。地衣红染色图像结果分析及直方图的分析表明:生长激素微胶囊组胶原纤维产生促进骨小梁提前形成,进而骨折处骨性骨痂的提前愈合和髓腔的提前贯通。结论:生长激素-海藻酸钠-壳聚糖微胶囊口服能促进骨折修复愈合。     

β-TCP三维支架用于骨髓间充质干/基质细胞的研究最新进展

β-TCP(β-磷酸三钙)是一种近年来研究渐热的人工合成生物陶瓷材料,该原料制备的生物载体具有高生物相容性、良好生物吸收性、自发诱导骨细胞分化和扩增等优势,因此多用于骨损伤修复领域。将β-TCP作为三维支架材料的主料进行体外扩增骨髓间充质干/基质细胞(MSC)并进行成骨分化检测或移植修复骨损伤的研究已取得一定进展。无论是以β-TCP为支架影响MSC成骨分化的因素和工艺基础研究;还是在移植修复骨损伤方面;甚至三维灌注进行工业化扩增,均显示该材料颇具应用价值。拟围绕上述领域简要介绍和评述国内外近年来的最新研究进展。     

新型硼酸盐生物玻璃修复兔股骨缺损的实验研究

目的:通过观察3种生物玻璃材料在修复兔股骨缺损中的差异,来比较新型硼酸盐生物玻璃球粒与生物玻璃球粒和生物玻璃颗粒成骨能力和降解性能的差异,为其进一步应用于临床提供理论依据.方法:成年新西兰大白兔18只,双侧股骨髁部制造直径0.6 cm,深1.2 cm的贯穿型缺损.根据缺损部位植入材料的不同随机分为3组,每组6只12侧:实验对照组(A组)植入生物玻璃颗粒(The NovaBone Bioactive Glass Morsels),实验组(B组)植入生物玻璃球粒(The NovaBone Bioactive Glass Spheres),实验组(C组)植入硼酸盐玻璃球粒(The Borate Glass Morsels)三种材料,于术后第6周,第12周取材,通过大体观察,组织病理学染色来评价新型生物活性玻璃的骨缺损修复能力和降解性能.结果:第6周时,ABC组均可见有新骨生成,并且向材料内部生长.在第12周时,ABC组成骨量显著增多,而且可见成熟的骨小梁塑形.组织切片定量分析:1、成骨能力比较:术后6周,12周时,新生骨量,B组和C组多于A组(P＜0.05),且C组多于B组(P＜0.05).术后12周与6周比较,ABC三组新生骨显著增多,(P＜0.05).2、降解性能比较:术后6周,12周时,残余材料量,B组和C组少于A组(P＜0.05),且C组少于B组(P＜0.05).术后12周与6周比较,ABC三组残余材料显著减少,(P＜0.05).结论:具有球体外观设计的新型硼酸盐玻璃球粒与其它两种材料相比,不仅具有良好的成骨能力,而且具有良好降解性能,能有效的修复腔隙性骨缺损,有望成为新型骨缺损修复材料.     

Ameliorative Effect of Bone Marrow-Derived Stem Cells on Injured Liver of Mice Infected with Schistosoma mansoni

The technique of stem cells or hepatocytes transplantation has recently improved in order to bridge the time before whole-organ liver transplantation. In the present study, unfractionated bone marrow stem cells (BMSCs) were harvested from the tibial and femoral marrow compartments of male mice, which were cultured in Dulbecco''s modified Eagle''s medium (DMEM) with and without hepatocyte growth factor (HGF), and then transplanted into Schistosoma mansoni-infected female mice on their 8th week post-infection. Mice were sacrificed monthly until the third month of bone marrow transplantation, serum was collected, and albumin concentration, ALT, AST, and alkaline phosphatase (ALP) activities were assayed. On the other hand, immunohistopathological and immunohistochemical changes of granuloma size and number, collagen content, and cells expressing OV-6 were detected for identification of liver fibrosis. BMSCs were shown to differentiate into hepatocyte-like cells. Serum ALT, AST, and ALP were markedly reduced in the group of mice treated with BMSCs than in the untreated control group. Also, granuloma showed a marked decrease in size and number as compared to the BMSCs untreated group. Collagen content showed marked decrease after the third month of treatment with BMSCs. On the other hand, the expression of OV-6 increased detecting the presence of newly formed hepatocytes after BMSCs treatment. BMSCs with or without HGF infusion significantly enhanced hepatic regeneration in S. mansoni-induced fibrotic liver model and have pathologic and immunohistopathologic therapeutic effects. Also, this new therapeutic trend could generate new hepatocytes to improve the overall liver functions.     

Combination of bone tissue engineering and BMP-2 gene transfection promotes bone healing in osteoporotic rats

OBJECTIVE: The aim of this study was to develop a feasible approach to promote bone healing in osteoporotic rats using autogenous bone tissue-engineering and gene transfection of human bone morphogenetic protein 2 (hBMP-2). METHODS: Bone marrow stromal cells (BMSCs) from the left tibia of osteoporotic rats were transfected with the hBMP-2 gene in vitro which was confirmed by immunohistochemistry, in situ hybridization and Western blotting. Autogenous transfected or untransfected BMSCs were seeded on macroporous coral hydroxyapatite (CHA) scaffolds. Each cell-scaffold construct was implanted into a defect site which was created in the ramus of the mandible of osteoporotic rats. Four or eight weeks after implantation in situ hybridization was performed in BMSCs transfected with hBMP-2, X-ray examinations, histological and histomorphological analyses were used to evaluate the effect of tissue-engineered bone on osseous defect repair. RESULTS: Newly formed bone was observed at the margin of the defect 4 weeks after implantation with BMSCs transfected with BMP-2. Mature bone was observed 8 weeks after treatment. In the control group there was considerably less new bone and some adipose tissue was observed at the defect margins 8 weeks after implantation. CONCLUSIONS: Autogenous cells transfected with hBMP-2 promote bone formation in osteoporotic rats. BMSC-mediated BMP-2 gene therapy used in conjunction with bone tissue engineering may be used to successfully treat bone defects in osteoporotic rats. This method provides a powerful tool for bone regeneration and other tissue engineering.     

The bone-forming effects of HIF-1α-transduced BMSCs promote osseointegration with dental implant in canine mandible

The presence of insufficient bone volume remains a major clinical problem for dental implant placement to restore the oral function. Gene-transduced stem cells provide a promising approach for inducing bone regeneration and enhancing osseointegration in dental implants with tissue engineering technology. Our previous studies have demonstrated that the hypoxia-inducible factor-1α (HIF-1α) promotes osteogenesis in rat bone mesenchymal stem cells (BMSCs). In this study, the function of HIF-1α was validated for the first time in a preclinical large animal canine model in term of its ability to promote new bone formation in defects around implants as well as the osseointegration between tissue-engineered bone and dental implants. A lentiviral vector was constructed with the constitutively active form of HIF-1α (cHIF). The ectopic bone formation was evaluated in nude mice. The therapeutic potential of HIF-1α-overexpressing canine BMSCs in bone repair was evaluated in mesi-implant defects of immediate post-extraction implants in the canine mandible. HIF-1α mediated canine BMSCs significantly promoted new bone formation both subcutaneously and in mesi-implant defects, including increased bone volume, bone mineral density, trabecular thickness, and trabecular bone volume fraction. Furthermore, osseointegration was significantly enhanced by HIF-1α-overexpressing canine BMSCs. This study provides an important experimental evidence in a preclinical large animal model concerning to the potential applications of HIF-1α in promoting new bone formation as well as the osseointegration of immediate implantation for oral function restoration.     

Dimethyloxaloylglycine Improves Angiogenic Activity of Bone Marrow Stromal Cells in the Tissue-Engineered Bone

One of the big challenges in tissue engineering for treating large bone defects is to promote the angiogenesis of the tissue-engineered bone. Hypoxia inducible factor-1α (HIF-1α) plays an important role in angiogenesis-osteogenesis coupling during bone regeneration, and can activate a broad array of angiogenic factors. Dimethyloxaloylglycine (DMOG) can activate HIF-1α expression in cells at normal oxygen tension. In this study, we explored the effect of DMOG on the angiogenic activity of bone mesenchymal stem cells (BMSCs) in the tissue-engineered bone. The effect of different concentrations of DMOG on HIF-1a expression in BMSCs was detected with western blotting, and the mRNA expression and secretion of related angiogenic factors in DMOG-treated BMSCs were respectively analyzed using qRT-PCR and enzyme linked immunosorbent assay. The tissue-engineered bone constructed with β-tricalcium phosphate (β-TCP) and DMOG-treated BMSCs were implanted into the critical-sized calvarial defects to test the effectiveness of DMOG in improving the angiogenic activity of BMSCs in the tissue-engineered bone. The results showed DMOG significantly enhanced the mRNA expression and secretion of related angiogenic factors in BMSCs by activating the expression of HIF-1α. More newly formed blood vessels were observed in the group treated with β-TCP and DMOG-treated BMSCs than in other groups. And there were also more bone regeneration in the group treated with β-TCP and DMOG-treated BMSCs. Therefore, we believed DMOG could enhance the angiogenic activity of BMSCs by activating the expression of HIF-1α, thereby improve the angiogenesis of the tissue-engineered bone and its bone healing capacity.     

Suppression of mTOR signaling pathway promotes bone marrow mesenchymal stem cells differentiation into osteoblast in degenerative scoliosis: in vivo and in vitro

To investigate the role of mTOR signaling pathway in bone marrow mesenchymal stem cells (BMSCs) differentiation into osteoblast in degenerative scoliosis (DS). The rat model of DS was established. Thirty-two Sprague–Dawley (SD) rats were selected and divided into the normal control group, the positive control group (normal rats injected with rapamycin), the negative control group (DS rats injected with PBS) and the experiment group (DS rats injected with rapamycin). H&E staining was performed to observe the osteogenesis of scoliosis. The BMSCs were obtained and assigned into seven groups: the normal control group, the positive control group, the negative control group and 1.0/10.0/100.0/1000.0 nmol/L experiment groups. Flow cytometry was conducted to testify cell cycle. The mRNA and protein expressions of mTOR and osteoblastic differentiation markers were measured by qRT-PCR and western blotting. In vivo, compared with the negative control group, bone trabecular area and the number of differentiated bone cells were significantly increased in the experiment groups. In vitro, at 24 and 48 h after rapamycin treatment, compared with the negative control group, BMSCs at G0/G1 stage increased, but BMSCs at S stage decreased in the 1.0/10.0/100.0/1000.0 nmol/L experiment groups; the expressions of mTOR and p70-S6K1 proteins were reduced in the 1.0/10.0/100.0/1000.0 nmol/L experiment groups, while ALP activity, OC levels, calcium deposition, Co1-I protein expression and the mRNA expressions of OC and Co1-I were significantly increased. Suppression of mTOR signaling pathway by rapamycin could promote BMSCs differentiation into osteoblast in DS.     

Placenta- versus bone-marrow-derived mesenchymal cells for the repair of segmental bone defects in a rabbit model

Tissue-engineered bones (TEBs) constructed with bone-marrow-derived mesenchymal stem cells (BMSCs) seeded on biomaterial scaffolds have achieved good results for bone defect repair in both animal experiments and clinical trials. This has been limited, however, by the source and quantity of BMSCs. We here explored TEBs constructed by placenta-derived mesenchymal stem cells (PMSCs) and compared their effect for the repair of critical-sized segmental osteoperiosteal defects with TEBs constructed with BMSCs. PMSCs were isolated from rabbit placenta by gradient centrifugation and in vitro monolayer culturing, and BMSCs were isolated from the hindlimb bone marrow of newborn rabbit. Primary cultured PMSCs and BMSCs were uniformly in a spindle shape. Immunocytochemistry indicated that both types of cells are positive for CD44 and CD105, and negative for CD34 and CD40L, confirming that they are mesenchymal stem cells. BrdU-labeled PMSCs and BMSCs were respectively co-cultured with bio-derived bone materials to construct TEBs in vitro. Critical-sized segmental osteoperiosteal defects of radii were created in 24 rabbits by surgery. The defects were repaired with TEBs constructed with PMSCs and BMSCs. The results showed that TEBs constructed by both PMSCs and BMSCs could repair the osteoperiosteal defects in a 'multipoint' manner. Measurement of radiography, histology, immunohistochemistry, alkaline phosphatase activity, osteocalcin assaying and biomechanical properties have found no significant difference between the two groups at 2, 4, 8 and 12 weeks after the transplantation (P > 0.05). Taken together, our results indicate that PMSCs have similar biological characteristics and osteogenic capacity to BMSCs and can be used as a new source of seeding cells for TEBs.     

Utility of tricalcium phosphate and osteogenic matrix cell sheet constructs for bone defect reconstruction

AIM: To determine the effects of transplanting osteogenic matrix cell sheets and beta-tricalcium phosphate (TCP) constructs on bone formation in bone defects.METHODS: Osteogenic matrix cell sheets were prepared from bone marrow stromal cells (BMSCs), and a porous TCP ceramic was used as a scaffold. Three experimental groups were prepared, comprised of TCP scaffolds (1) seeded with BMSCs; (2) wrapped with osteogenic matrix cell sheets; or (3) both. Constructs were implanted into a femoral defect model in rats and bone growth was evaluated by radiography, histology, biochemistry, and mechanical testing after 8 wk.RESULTS: In bone defects, constructs implanted with cell sheets showed callus formation with segmental or continuous bone formation at 8 wk, in contrast to TCP seeded with BMSCs, which resulted in bone non-union. Wrapping TCP constructs with osteogenic matrix cell sheets increased their osteogenic potential and resulting bone formation, compared with conventional bone tissue engineering TCP scaffolds seeded with BMSCs. The compressive stiffness (mean ± SD) values were 225.0 ± 95.7, 30.0 ± 11.5, and 26.3 ± 10.6 MPa for BMSC/TCP/Sheet constructs with continuous bone formation, BMSC/TCP/Sheet constructs with segmental bone formation, and BMSC/TCP constructs, respectively. The compressive stiffness of BMSC/TCP/Sheet constructs with continuous bone formation was significantly higher than those with segmental bone formation and BMSC/TCP constructs.CONCLUSION: This technique is an improvement over current methods, such as TCP substitution, and is useful for hard tissue reconstruction and inducing earlier bone union in defects.     

Inhibited Wnt Signaling Causes Age-Dependent Abnormalities in the Bone Matrix Mineralization in the Apert Syndrome FGFR2S252W/+ Mice

Apert syndrome (AS) is a type of autosomal dominant disease characterized by premature fusion of the cranial sutures, severe syndactyly, and other abnormalities in internal organs. Approximately 70% of AS cases are caused by a single mutation, S252W, in fibroblast growth factor receptor 2 (FGFR2). Two groups have generated FGFR2 knock-in mice Fgfr2^S252W/+ that exhibit features of AS. During the present study of AS using the Fgfr2^S252W/+ mouse model, an age-related phenotype of bone homeostasis was discovered. The long bone mass was lower in 2 month old mutant mice than in age-matched controls but higher in 5 month old mutant mice. This unusual phenotype suggested that bone marrow-derived mesenchymal stem cells (BMSCs), which are vital to maintain bone homeostasis, might be involved. BMSCs were isolated from Fgfr2^S252W/+ mice and found that S252W mutation could impair osteogenic differentiation BMSCs but enhance mineralization of more mature osteoblasts. A microarray analysis revealed that Wnt pathway inhibitors SRFP1/2/4 were up-regulated in mutant BMSCs. This work provides evidence to show that the Wnt/β-catenin pathway is inhibited in both mutant BMSCs and osteoblasts, and differentiation defects of these cells can be ameliorated by Wnt3a treatment. The present study suggested that the bone abnormalities caused by deregulation of Wnt pathway may underlie the symptoms of AS.