Bone Research
·
2022
·Vol. 10
·期 1
·1-12
·
IF 13.362
Kong Ning,Yang Hang,Tian Run,Liu Guanzhi,Li Yiyang,Guan Huanshuai,Wei Qilu,Du Xueshan,Lei Yutian,Li Zhe,Cao Ruomu,Zhao Yiwei,Wang Xiaohui,Wang Kunzheng,Yang Pei
Core decompression (CD) with the elimination of osteonecrotic bone is the most common strategy for treating early-stage nontraumatic osteonecrosis of the femoral head (ONFH). Adjuvant treatments are widely used in combination with CD as suitable methods of therapy. Existing augmentations have to be fabricated in advance. Here, we report a novel injectable glycerin-modified polycaprolactone (GPCL) that can adapt to the shape of the CD cavity. GPCL shows great flowability at 52.6 °C. After solidification, its compressive modulus was 120 kPa at body temperature (37 °C). This excellent characteristic enables the polymer to provide mechanical support in vivo. In addition, GPCL acts as a carrier of the therapeutic agent zoledronic acid (ZA), demonstrating sustained release into the CD region. ZA-loaded GPCL was injected into ONFH lesions to treat early-stage nontraumatic cases. Compared to that in the CD group, CD+ZA-loaded GPCL injection preserved bone density and increased the collagen level in the femoral head. At the interface between the GPCL and CD tunnel wall, osteogenesis was significantly promoted. In addition, morphological evaluations revealed that the femoral heads in the CD+ZA-GPCL group exhibited improved pressure resistance. These results suggest a strategy effective to preserve the bone density of the femoral head, thus decreasing the possibility of femoral head collapse. This novel injectable polymer has, therefore, considerable potential in clinical applications.
研究领域:
生物医学工程
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骨科
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材料科学
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药剂学
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2024
·
IF 3.8
Li Chen,Liu Jikun,Sheng Yiqi,Wang Yinghao,Jia Lan,Zhang Yinguang,Li Jiantao,Di Shuangshuang,Nie Honggang,Han Yehua
Osteonecrosis of the femoral head (ONFH) is a common orthopedic disease characterized by disability and deformity. To better understand ONFH at molecular level and to explore the possibility of early diagnosis, instead of diagnosis based on macroscopic spatial characteristics, a matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) method was developed for ONFH disease for the first time. The most challenging step for ONFH MSI is to deal with human bone tissues which are much harder than the other biological samples studied by the reported MSI studies. In this work, the MSI sectioning method of hard bone tissues was established using tender acids and a series of test criteria. Small-molecule metabolites, such as lipids and amino acids, were detected in bone sections, realizing the in situ detection of spatial distribution of biometabolites. By comparing the distribution of metabolites from different regions of normal femoral head, ONFH bone tissue (ONBT), and adjacent ONFH bone tissue (ANBT), the whole process of femoral head from normal stage to necrosis was monitored and visualized at molecular level. Moreover, this developed MSI method was used for metabolomics study of ONFH. 72 differential metabolites were identified, suggesting that disturbances in energy metabolism and lipid metabolism affected the normal life activities of osteoblasts and osteoclasts. This study provides new perspectives for future pathological studies of ONFH.
研究领域:
骨科
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分子生物学
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医学影像学
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产品关联
DOI
PubMed
高影响因子
Stem Cell Research & Therapy
·
2021
·Vol. 12
·期 1
·1-16
·
IF 6.832
Zhou Meiling,Xi Jiaoya,Cheng Yaofeng,Sun Denglong,Shu Peng,Chi Shuiqing,Tian Shuo,Ye Shunan
Background Cellular therapy based on mesenchymal stem cells (MSCs) is a promising novel therapeutic strategy for the osteonecrosis of the femoral head (ONFH), which is gradually becoming popular, particularly for early-stage ONFH. Nonetheless, the MSC-based therapy is challenging due to certain limitations, such as limited self-renewal capability of cells, availability of donor MSCs, and the costs involved in donor screening. As an alternative approach, MSCs derived from induced pluripotent stem cells (iPSCs), which may lead to further standardized-cell preparations. Methods In the present study, the bone marrow samples of patients with ONFH ( n = 16) and patients with the fracture of the femoral neck ( n = 12) were obtained during operation. The bone marrow-derived MSCs (BMSCs) were isolated by density gradient centrifugation. BMSCs of ONFH patients (ONFH-BMSCs) were reprogrammed to iPSCs, following which the iPSCs were differentiated into MSCs (iPSC-MSCs). Forty adult male rats were randomly divided into following groups ( n = 10 per group): (a) normal control group, (b) methylprednisolone (MPS) group, (c) MPS + BMSCs treated group, and (d) MPS + iPSC-MSC-treated group. Eight weeks after the establishment of the ONFH model, rats in BMSC-treated group and iPSC-MSC-treated group were implanted with BMSCs and iPSC-MSCs through intrabone marrow injection. Bone repair of the femoral head necrosis area was analyzed after MSC transplantation. Results The morphology, immunophenotype, in vitro differentiation potential, and DNA methylation patterns of iPSC-MSCs were similar to those of normal BMSCs, while the proliferation of iPSC-MSCs was higher and no tumorigenic ability was exhibited. Furthermore, comparing the effectiveness of iPSC-MSCs and the normal BMSCs in an ONFH rat model revealed that the iPSC-MSCs was equivalent to normal BMSCs in preventing bone loss and promoting bone repair in the necrosis region of the femoral head. Conclusion Reprogramming can reverse the abnormal proliferation, differentiation, and DNA methylation patterns of ONFH-BMSCs. Transplantation of iPSC-MSCs could effectively promote bone repair and angiogenesis in the necrosis area of the femoral head.
研究领域:
干细胞生物学
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骨科
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再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
KAOHSIUNG JOURNAL OF MEDICAL SCIENCES
·
2025
·
IF 3.1
Qing Su,Jia Chen
Steroid-induced osteonecrosis of the femoral head (SIONFH) is a debilitating orthopedic condition. This study investigated the mechanism of Tanshinone I (TsI) in SIONFH modulating apoptosis in SIONFH via the PI3K/AKT/mTOR pathway. A SIONFH rat model was treated with TsI and a PI3K activator. Bone mineral density (BMD), bone volume/total volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and trabecular separation (Tb.Sp) were determined by microCT. Empty lacunae count, Osteopontin, and apoptosis of the femoral head tissues were assessed. Levels of Bax, cleaved-caspase-3, Bcl-2, and AKT, PI3K, and mTOR phosphorylation in femoral head tissues were determined by Western blot. SIONFH rats exhibited decreased BMD, BV/TV, Tb.N, and Tb.Th, increased Tb.Sp, reduced Osteopontin-positive cells, increased empty lacunae rate, and TUNEL and Osteopontin co-positive cells, elevated Bax and cleaved-caspase-3 protein levels, and diminished Bcl-2 protein expression. TsI promoted osteogenesis, attenuated SIONFH, and reduced apoptosis in SIONFH rats. TsI inhibited AKT, PI3K, and mTOR phosphorylation levels in the femoral head tissues of SIONFH rats, thereby repressing the PI3K/AKT/mTOR pathway activation. Activating the PI3K/AKT/mTOR pathway partially reversed TsI's effect in rats. Collectively, TsI limited the PI3K/AKT/mTOR pathway activation to reduce osteocyte apoptosis in SIONFH rats, which provided potential therapeutic insights for SIONFH treatment.
研究领域:
骨科学
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分子药理学
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细胞生物学
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信号转导
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中医药学
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产品关联
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2024
·Vol. 27
·期 5
·1-10
·
IF 2.4
Jiaqi Shi,Li Chen,Xu Wang,Xin Ma
Steroid‑induced osteonecrosis of the femoral head (ONFH) is a serious complication caused by long‑term or excessive use of glucocorticoids. The present study aimed to ascertain the effects of tripartite motif‑containing protein 21 (TRIM21) on the process of steroid‑induced ONFH and its hidden action mechanism. TRIM21 expression in dexamethasone (Dex)‑treated mouse MC3T3‑E1 preosteoblast cells was examined using reverse transcription‑quantitative PCR and western blotting. The Cell Counting Kit‑8 (CCK‑8) method and lactate dehydrogenase release assay were used to respectively measure cell viability and injury. Flow cytometry analysis was used to assay cell apoptosis. Caspase 3 activity was evaluated using a specific assay, while alkaline phosphatase and Alizarin red S staining were used to evaluate osteogenesis. 2,7‑dichloro‑dihydrofluorescein diacetate fluorescence probe was used to estimate reactive oxygen species generation. Specific assay kits were used to appraise oxidative stress levels. In addition, the expression of apoptosis‑, osteogenic differentiation‑ and Kelch‑like ECH‑associated protein 1 (Keap1)/nuclear factor erythroid 2‑related factor 2 (Nrf2) signaling‑associated proteins was assessed using western blotting. In Nrf2 inhibitor (ML385)‑pretreated MC3T3‑E1 cells exposed to Dex, cell apoptosis, osteogenesis and oxidative stress were detected again as aforementioned. Results revealed that TRIM21 expression was raised in Dex‑induced MC3T3‑E1 cells and TRIM21 deletion improved the viability and osteogenic differentiation, whereas it hampered the oxidative stress and apoptosis in MC3T3‑E1 cells with Dex induction. In addition, silencing of TRIM21 activated Keap1/Nrf2 signaling. Moreover, ML385 partially abrogated the effects of TRIM21 depletion on the oxidative stress, apoptosis and osteogenic differentiation in MC3T3‑E1 cells exposed to Dex. In conclusion, TRIM21 silencing might activate Keap1/Nrf2 signaling to protect against steroid‑induced ONFH.
研究领域:
骨科
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Orthopaedic Surgery
·
2022
·Vol. 14
·期 10
·2669-2681
·
IF 2.279
Bo-yong Jang,Shi-bing Guo,Rui Bai,Wan-lin Liu,Yu-lin Gong,Zhen-qun Zhao
Objective To study the relationship between vascular endothelial cells (VEC) and autophagy, and its regulatory mechanism in steroid-induced avascular necrosis of the femoral head (SANFH). Methods In cell experiment, VEC were isolated and cultured from the femoral head of Sprague–Dawley rats and divided into three groups: blank control group (Ctrl), methylprednisolone group (MP), and methylprednisolone+mTOR-shRNA group (MP + shmTOR). The autophagy formation was observed by transmission electron microscope. The mRNA expression of PI3K, Akt, mTOR, Beclin1 and MAP1LC3 was detected by RT-PCR and the protein expression was detected by Western blot and immunofluorescence. Expression of the damage marker 6-keto-PGF1α was detected by the ELISA method. In vivo experiment, after establishing the model, the grouping method was the same as cell experiment. Autophagosomes were observed by same method, and the expression of related factors was detected by the same method in cell experiment. Results In the cell experiment, autophagosomes in the MP group were significantly lower than in the Ctrl group, and the autophagosomes in the MP + shmTOR group were intermediate between two groups ( P < 0.05). The mRNA expression levels of PI3K, Akt and mTOR in the MP group were significantly higher than in the Ctrl group, while the MP+ shmTOR group presented intermediate levels between these groups (average gray value were 3837.90, 2996.30, 3005.60, F = 428.64, P < 0.05). MRNA expression levels of Beclin1 and MAP1LC3 in the MP group were significantly lower than that in Ctrl group ( P < 0.05). The content of 6-keto-PGF1α in the MP + shmTOR group was higher than in the Ctrl group and lower than in the MP group at the evaluated time intervals (average absorbance value were 104.98, 206.83, 145.91, F = 352.83, P < 0.01). In vivo experiment, the content of 6-Keto-PGF1α in the hormone group increased as time went on; the mTOR-si group was higher than that in control group, but lower than that in the hormone group ( P < 0.01). The mRNA expressions of Beclin1 and MAP1LC3 in the control group were higher than those in the hormone group, while the mRNA expressions of PI3K, Akt and mTOR were lower than those in the mTOR-si group ( P < 0.05). Conclusion The steroid inhibited the physiological protective effect of autophagy on SANFH by increasing the expression of PI3K/Akt/mTOR signaling pathway related factors and decreasing the expression of Beclin1 and MAP1LC3 in the femoral head VEC.
研究领域:
药理学
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细胞生物学
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骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Physiology
·
2018
·
IF 3.394
Deng Shuang,Zhou Jian-Lin,Fang Hong-Song,Nie Zhi-Gang,Chen Sen,Peng Hao
Glucocorticoids intake has become the most common pathogenic factor for osteonecrosis of the femoral head (ONFH). Annually, tens of millions of patients suffer from pain related to ONFH. Researchers have proposed several underlying mechanisms of ONFH, including osteocyte apoptosis, cell differentiation disorder, and angiogenesis hindrance. Sesamin, isolated from Sesamum indicum seeds, was reported could affect osteocyte inflammation and differentiation in osteoarthritis and osteoporosis. We investigated the underlying influence of sesamin on ONFH rat model. Fifteen male Sprague-Dawley rats were randomly divided into three groups. The ONFH model group only received the methylprednisolone (MPS) and lipopolysaccharide (LPS) injection to promote the development of ONFH. The sesamin treatment group was injected with sesamin, MPS, and LPS. The control group was untreated. Rats from above groups were sacrificed 4 weeks later. The effect of sesamin on ONFH rats was validated by H&E staining. TUNEL staining showed that femoral head necrosis was attenuated by sesamin. Furthermore, the phosphorylation of Akt was increased and the downstream cellular apoptosis signal pathway was inhibited. Intracellular ROS level was decreased after sesamin treatment. In conclusion, our findings suggest that sesamin protects the femoral head from osteonecrosis by inhibiting ROS-induced osteoblast apoptosis.
研究领域:
药理学
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骨科
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELL PROLIFERATION
·
2020
·Vol. 53
·期 8
·e12871
·
IF 5.753
Hongping Yu,Pei Liu,Daoyu Zhu,Junhui Yin,Qianhao Yang,Yigang Huang,Yixuan Chen,Changqing Zhang,Youshui Gao
Objectives Osteonecrosis of the femoral head (ONFH), largely caused by alcohol abuse, is a refractory bone disease characterized by the impaired capacity of osteogenic differentiation of bone mesenchymal stem cells (BMSCs), as well as the disordered adipocyte accumulation. Chrysophanic acid (CPA) is a natural anthraquinone which has lipid regulation and bone protection capacity. The aim of this study was to reveal the potential function of CPA and the underlying mechanisms for the alcohol-induced ONFH. Materials and Methods The effects of alcohol and CPA on BMSCs were investigated by cell proliferation, induced differentiation assays and immunofluorescent staining. Meanwhile, the function of PI3K/AKT and AMPK pathway was investigated in the process of osteogenic and adipogenic differentiation, respectively. Furthermore, we established the rat model of alcohol-induced ONFH to reveal the pharmacotherapeutic effect of CPA in vivo using radiographical and histopathological methods. Results In vitro, alcohol significantly inhibited the proliferation and osteogenic differentiation of BMSCs but stimulated the adipogenic differentiation. However, CPA could counteract the anti-osteogenesis of alcohol partly via PI3K/AKT pathway and retard the promotion of alcohol-induced adipogenesis via AMPK pathway. In vivo, radiographical and histopathological findings showed that CPA could alleviate alcohol-induced ONFH and substantially restore the bone volume. Conclusions We demonstrated that CPA ameliorated alcohol-induced ONFH possibly via regulating the differentiation tendency of BMSCs. Hence, CPA may become a beneficial herb extract to alleviate alcohol-induced ONFH.
研究领域:
药理学
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骨科
·
干细胞研究
✓ 已验证
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Zherui Fu,Yiwen Xu,Fangqi Xu,Haoyu Zhou,Na Lin,Ning Zhang,Feng Lin
The incidence of steroid-induced osteonecrosis of the femoral head (SONFH) is increasing annually; however, the underlying pathological mechanism remains unclear, which is an obstacle to its effective treatment. The negative effect of immune infiltration on the physiological activity of focal stem cells is one potential mechanism that has attracted attention. It is difficult to simulate the complex regulation of the interaction system between immune cells and stem cells using a single regulation method. In this study, we demonstrated that the immune infiltration of T helper 17 (Th17) cells plays an important role in the progression of SONFH. Based on this finding, we developed an injectable hydrogel system with both physical and chemical synergistic regulatory properties to enhance the activity of stem cells using electrical stimulation. This treatment was designed to prevent the infiltration of Th17 cells by regulating the physiological function of stem cells and blocking the negative effect of Th17 cells on stem cells pharmacologically. Thus, the dual synergistic regulation of immune infiltration at the lesion site of SONFH enhanced the physiological activity and function of the stem cells, thereby improving the therapeutic effect of SONFH. This hydrogel system provides insight for the future development of multifactorial regulatory systems and provides a strategy for the treatment of SONFH.
研究领域:
医学
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生物材料学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
American Journal of Translational Research
·
2020
·
IF 3.375
Runzi Gao,Wenhui Ji,Tianwei Xia,Yanxing Fan,Wei Wei,Le Shi,Jinzhu Liu,Chao Zhang,Lezhen Xue,Jirong Shen
Osteonecrosis of the femoral head (ONFH) is a common disorder that may be idiopathic, caused by trauma, or associated with alcohol or glucocorticoid use. The goals of early treatment include delaying or avoiding hip replacement, but there are no effective treatments for early-stage disease. The aim of the present study was to evaluate the effects of treatment with 3D-printed porous titanium alloy scaffold combined with daily intraperitoneal trans-cinnamaldehyde (TCA) in a dog model of ONFH. Four weeks after creation of the ONFH model, MRI examination of the femoral head showed the characteristic “double line sign” of ONFH, verifying the validity of our model. After another 12 weeks, femoral head specimens were harvested and examined by gross inspection; micro-computed tomography; histologic staining (hematoxylin and eosin; Masson); immunohistochemical analysis and quantitative real-time polymerase chain reaction analysis. Gross inspection of the femoral head in untreated ONFH animals at 16 weeks after model creation showed pale, exfoliating articular cartilage and disordered trabecular bone. Treatment with 3D-printed titanium alloy porous scaffold combined with TCA ameliorated the pathologic ONFH changes and significantly reduced inmature bone tissue as well as imature collagen in the femoral head, as shown by Masson staining. This treatment also increased VEGF, BMP2, β-catenin, b-FGF, and RUNX2 expression and decreased PPARγ expression, compared with untreated ONFH. In conclusion, 3D-printed titanium alloy porous scaffold combined with TCA can effectively improve ONFH, which may be related to local repair. This provides the theoretical basis for a new treatment strategy for ONFH.
研究领域:
骨科
·
再生医学
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药理学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Stem Cells International
·
2021
·
IF 5.443
Zhipeng Huang,Zhe Zhao,Jun Lang,Wantao Wang,Yinsheng Fu,Wenbo Wang
Super activated platelet lysate (sPL) is a derivative of platelet-rich plasma (PRP) that contains high levels of several growth factors. In this study, we synthesized a temperature-sensitive hydrogel that contained temperature-sensitive Poly(DL-lactide-glycolide-glycolide acid) (PLGA), SrCl2, and HA, and loaded it with different concentrations of sPL. The hydrogel showed satisfactory encapsulation efficiency and release of the growth factors in a sustained manner, indicating its suitability as a drug carrier. The sPL-loaded hydrogel was inserted into the necrotic femoral head of a rat model and core decompression was applied and resulted in significantly accelerated bone repair and regeneration. Therefore, encapsulation of sPL in a hydrogel scaffolding may be an effective strategy for treating femoral head necrosis.
研究领域:
医学
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生物材料学
·
骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
American Journal of Translational Research
·
2021
·
IF 4.06
Lexiang Li,Yi Chen,Qiwei Fu,Haishan Wu,Yiqin Zhou,Jiahua Shao,Jun Wu,Yaguang Han,Qirong Qian
Background: Tissue engineering is widely applied to treat osteochondral damage in osteoarthritis (OA). However, the superposition of seed cells, material scaffolds, inducing factors, and microenvironmental factors limit their practical application. We intended to develop a novel tissue engineering method for improving the repairment of osteochondral damage and to discuss its effect on repairing osteochondral defects. Methods: The combined decellularization methods of physics, chemistry and enzymes were used to decellularize rabbit rib cartilage and articular cartilage, and rabbit decellularizated osteochondral composite scaffolds were prepared. The structure and organization of the scaffolds were analyzed. We extracted and identified infrapatellar fat pad stem cells (IPFP-SCs) from healthy rabbits and OA rabbit, which were different in viability, migration, osteogenic and chondrogenic differentiation. Finally, a variety of decellularizated bone cartilage composite scaffolds were loaded with rabbit IPFP-SC for in vitro and in vivo studies. Results: The decellularization effect was strong, and the organic ingredients were lost. The layered scaffold showed lower density, greater porosity, larger pore size and water absorption than the whole scaffold, but the mechanical properties of the two scaffolds were low. IPFP-SCs were successfully extracted, and the migration and cartilage ability of IPFP-SCs in OA group were weak. The decellularized scaffold showed a high biocompatibility. The structure and composition of osteochondral promoted osteogenic differentiation and chondrogenic differentiation of IPFP-SCs. Moreover, the decellularized extracellular matrix loaded with IPFP-SC had the strongest repairing effect. Conclusion: The decellularized extracellular matrix loaded with IPFP-SC showed a better repair effect on rabbit osteochondral defects.
研究领域:
组织工程
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骨科
·
干细胞研究
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）