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1.
Diagnostics (Basel) ; 14(11)2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38893618

RESUMO

Artificial intelligence (AI) refers to the science and engineering of creating intelligent machines for imitating and expanding human intelligence. Given the ongoing evolution of the multidisciplinary integration trend in modern medicine, numerous studies have investigated the power of AI to address orthopedic-specific problems. One particular area of investigation focuses on shoulder pathology, which is a range of disorders or abnormalities of the shoulder joint, causing pain, inflammation, stiffness, weakness, and reduced range of motion. There has not yet been a comprehensive review of the recent advancements in this field. Therefore, the purpose of this review is to evaluate current AI applications in shoulder pathology. This review mainly summarizes several crucial stages of the clinical practice, including predictive models and prognosis, diagnosis, treatment, and physical therapy. In addition, the challenges and future development of AI technology are also discussed.

2.
Int J Nanomedicine ; 19: 6319-6336, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38919773

RESUMO

Purpose: This research was to innovate a nanozyme-based therapeutic strategy that combines aggregation-induced emission (AIE) photosensitizers with copper nanozymes. This approach is designed to address the hypoxic conditions often found in bacterial infections and aims to boost the effectiveness of photodynamic therapy (PDT) by ensuring sufficient oxygen supply for reactive oxygen species (ROS) generation. Methods: Our approach involved the synthesis of dihydroxyl triphenyl vinyl pyridine (DHTPY)-Cu@zoledronic acid (ZOL) nanozyme particles. We initially synthesized DHTPY and then combined it with copper nanozymes to form the DHTPY-Cu@ZOL composite. The nanozyme's size, morphology, and chemical properties were characterized using various techniques, including dynamic light scattering, transmission electron microscopy, and X-ray photoelectron spectroscopy. We conducted a series of in vitro and in vivo tests to evaluate the photodynamic, antibacterial, and wound-healing properties of the DHTPY-Cu@ZOL nanozymes, including their oxygen-generation capacity, ROS production, and antibacterial efficacy against methicillin-resistant Staphylococcus aureus (MRSA). Results: The DHTPY-Cu@ZOL exhibited proficient H2O2 scavenging and oxygen generation, crucial for enhancing PDT in oxygen-deprived infection environments. Our in vitro analysis revealed a notable antibacterial effect against MRSA, suggesting the nanozymes' potential to disrupt bacterial cell membranes. Further, in vivo studies using a diabetic rat model with MRSA-infected wounds showed that DHTPY-Cu@ZOL markedly improved wound healing and reduced bacterial presence, underscoring its efficacy as a non-antibiotic approach for chronic infections. Conclusion: Our study suggests that DHTPY-Cu@ZOL is a highly promising approach for combating antibiotic-resistant microbial pathogens and biofilms. The biocompatibility and stability of these nanozyme particles, coupled with their improved PDT efficacy position them as a promising candidate for clinical applications.


Assuntos
Antibacterianos , Cobre , Staphylococcus aureus Resistente à Meticilina , Fotoquimioterapia , Fármacos Fotossensibilizantes , Infecção dos Ferimentos , Fotoquimioterapia/métodos , Animais , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Cobre/química , Cobre/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Imidazóis/química , Imidazóis/farmacologia , Piridinas/química , Piridinas/farmacologia , Ratos , Cicatrização/efeitos dos fármacos , Masculino , Humanos , Ratos Sprague-Dawley
3.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 38(6): 691-695, 2024 Jun 15.
Artigo em Chinês | MEDLINE | ID: mdl-38918189

RESUMO

Objective: To investigate the morphological characteristics of the glenohumeral joint (including the glenoid and coracoid) in the Chinese population and determine the feasibility of designing coracoid osteotomy based on the preoperative glenoid defect arc length by constructing glenoid defect models and simulating suture button fixation Latarjet procedure. Methods: Twelve shoulder joint specimens from 6 adult cadavers donated voluntarily were harvested. First, whether the coracoacromial ligament and conjoint tendon connected was anatomically observed and their intersection point was identified. The vertical distance from the intersection point to the coracoid, the maximum allowable osteotomy length starting from the intersection point, and the maximum osteotomy angle were measured. Next, the anteroinferior glenoid defect models of different degrees were randomly constructed. The arc length and area of the glenoid defect were measured. Based on the arc length of the glenoid defect of the model, the size of coracoid oblique osteotomy was designed and the actual length and angle of the coracoid osteotomy were measured. A limited osteotomy suture button fixation Latarjet procedure with the coracoacromial ligament and pectoralis minor preservation was performed and the position of coracoid block was observed. Results: All shoulder joint specimens exhibited crossing fibers between the coracoacromial ligament and the conjoint tendon. The vertical distance from the tip of the coracoid to the coracoid return point was 24.8-32.2 mm (mean, 28.5 mm). The maximum allowable osteotomy length starting from the intersection point was 26.7-36.9 mm (mean, 32.0 mm). The maximum osteotomy angle was 58.8°-71.9° (mean, 63.5°). Based on the anteroinferior glenoid defect model, the arc length of the glenoid defect was 22.6-29.4 mm (mean, 26.0 mm); the ratio of glenoid defect was 20.8%-26.2% (mean, 23.7%). Based on the coracoid block, the length of the coracoid osteotomy was 23.5-31.4 mm (mean, 26.4 mm); the osteotomy angle was 51.3°-69.2° (mean, 57.1°). There was no significant difference between the arc length of the glenoid defect and the length of the coracoid osteotomy ( P>0.05). After simulating the suture button fixation Latarjet procedure, the highest points of the coracoid block (suture loop fixation position) in all models located below the optimal center point, with the bone block concentrated in the anteroinferior glenoid defect position. Conclusion: The size of the coracoid is generally sufficient to meet the needs of repairing larger glenoid defects. The oblique osteotomy with preserving the coracoacromial ligament may potentially replace the traditional Latarjet osteotomy method.


Assuntos
Ligamentos Articulares , Osteotomia , Articulação do Ombro , Humanos , Osteotomia/métodos , Ligamentos Articulares/cirurgia , Articulação do Ombro/cirurgia , Articulação do Ombro/anatomia & histologia , Adulto , Masculino , Feminino , Ossos Pélvicos/cirurgia , Ossos Pélvicos/anatomia & histologia
4.
Adv Mater ; : e2402871, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38801111

RESUMO

Citrate-based biodegradable polymers have emerged as a distinctive biomaterial platform with tremendous potential for diverse medical applications. By harnessing their versatile chemistry, these polymers exhibit a wide range of material and bioactive properties, enabling them to regulate cell metabolism and stem cell differentiation through energy metabolism, metabonegenesis, angiogenesis, and immunomodulation. Moreover, the recent US Food and Drug Administration (FDA) clearance of the biodegradable poly(octamethylene citrate) (POC)/hydroxyapatite-based orthopedic fixation devices represents a translational research milestone for biomaterial science. POC joins a short list of biodegradable synthetic polymers that have ever been authorized by the FDA for use in humans. The clinical success of POC has sparked enthusiasm and accelerated the development of next-generation citrate-based biomaterials. This review presents a comprehensive, forward-thinking discussion on the pivotal role of citrate chemistry and metabolism in various tissue regeneration and on the development of functional citrate-based metabotissugenic biomaterials for regenerative engineering applications.

5.
Bioact Mater ; 36: 62-82, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38440323

RESUMO

Tendon-bone interface injuries pose a significant challenge in tissue regeneration, necessitating innovative approaches. Hydrogels with integrated supportive features and controlled release of therapeutic agents have emerged as promising candidates for the treatment of such injuries. In this study, we aimed to develop a temperature-sensitive composite hydrogel capable of providing sustained release of magnesium ions (Mg2+). We synthesized magnesium-Procyanidin coordinated metal polyphenol nanoparticles (Mg-PC) through a self-assembly process and integrated them into a two-component hydrogel. The hydrogel was composed of dopamine-modified hyaluronic acid (Dop-HA) and F127. To ensure controlled release and mitigate the "burst release" effect of Mg2+, we covalently crosslinked the Mg-PC nanoparticles through coordination bonds with the catechol moiety within the hydrogel. This crosslinking strategy extended the release window of Mg2+ concentrations for up to 56 days. The resulting hydrogel (Mg-PC@Dop-HA/F127) exhibited favorable properties, including injectability, thermosensitivity and shape adaptability, making it suitable for injection and adaptation to irregularly shaped supraspinatus implantation sites. Furthermore, the hydrogel sustained the release of Mg2+ and Procyanidins, which attracted mesenchymal stem and progenitor cells, alleviated inflammation, and promoted macrophage polarization towards the M2 phenotype. Additionally, it enhanced collagen synthesis and mineralization, facilitating the repair of the tendon-bone interface. By incorporating multilevel metal phenolic networks (MPN) to control ion release, these hybridized hydrogels can be customized for various biomedical applications.

6.
Int J Biol Macromol ; 254(Pt 2): 127912, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37939763

RESUMO

The repair of bone defects using grafts is commonly employed in clinical practice. However, the risk of infection poses a significant concern. Tissue engineering scaffolds with antibacterial functionalities offer a better approach for bone tissue repair. In this work, firstly, two kinds of nanoparticles were prepared using chitosan to complex with ciprofloxacin and BMP-2, respectively. The ciprofloxacin complex nanoparticles improved the dissolution efficiency of ciprofloxacin achieving a potent antibacterial effect and cumulative release reached 95 % in 7 h. For BMP-2 complexed nanoparticles, the release time points can be programmed at 80 h, 100 h or 180 h by regulating the number of coating chitosan layers. Secondly, a functional scaffold was prepared by combining the two nanoparticles with chitosan nanofibers. The microscopic nanofiber structure of the scaffold with 27.28 m2/g specific surface area promotes cell adhesion, high porosity provides space for cell growth, and facilitates drug loading and release. The multifunctional scaffold exhibits programmed release function, and has obvious antibacterial effect at the initial stage of implantation, and releases BMP-2 to promote osteogenic differentiation of mesenchymal stem cells after the antibacterial effect ends. The scaffold is expected to be applied in clinical bone repair and graft infection prevention.


Assuntos
Quitosana , Nanofibras , Nanopartículas , Osteogênese , Nanofibras/química , Quitosana/química , Preparações de Ação Retardada/farmacologia , Ciprofloxacina/farmacologia , Regeneração Óssea , Engenharia Tecidual , Alicerces Teciduais/química , Antibacterianos/farmacologia , Nanopartículas/química
7.
Int J Biol Macromol ; 257(Pt 1): 128481, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38042316

RESUMO

Osteoporosis is a systemic bone disease that is prone to fractures due to decreased bone density and bone quality, and delayed union or nonunion often occurs in osteoporotic fractures. Therefore, it is particularly important to develop tissue engineering materials to promote osteoporotic fracture healing. In this study, a series of biomimetic cryogels prepared from the decellularized extracellular matrix (dECM), methacrylate gelatin (GelMA), and carboxymethyl chitosan (CMCS) via unidirectional freezing, photo- and genipin crosslinking were applied for the regeneration of osteoporotic fractures. Specifically, dECM extracted from normal or osteoporotic rats was applied for the preparation of the cryogels, named as GC-Normal dECM or GC-OVX dECM, respectively. It was verified that the GC-Normal dECM demonstrated superior performance in promoting the proliferation of BMSCs isolated from osteoporotic rats (OVX-BMSCs), and the differentiation of OVX-BMSCs into osteoblasts both in vitro and in vivo. RNA sequencing and further verifications confirmed that GC-Normal dECM cryogel could scavenge the intracellular reactive oxygen species (ROS) in OVX-BMSCs to accelerate the regeneration of osteoporotic fracture by down-regulating the reactive oxygen species modulator 1 (Romo1). The results indicated that by regulating the ROS niche of OVX-BMSCs, biomimetic the GC-Normal dECM cryogel was expected to be a clinical candidate for repairing osteoporotic bone defects.


Assuntos
Osteoporose , Fraturas por Osteoporose , Ratos , Animais , Criogéis , Espécies Reativas de Oxigênio , Biomimética , Osteogênese
9.
Arthritis Res Ther ; 25(1): 217, 2023 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-37946278

RESUMO

BACKGROUND: The aggressive phenotype of fibroblast-like synoviocytes (FLS) has been identified as a contributing factor to the exacerbation of rheumatoid arthritis (RA) through the promotion of synovitis and cartilage damage. Regrettably, there is currently no effective therapeutic intervention available to address this issue. Recent research has shed light on the crucial regulatory role of R-spondin-2 (Rspo2) in cellular proliferation, cartilage degradation, and tumorigenesis. However, the specific impact of Rspo2 on RA remains poorly understood. We aim to investigate the function and mechanism of Rspo2 in regulating the aggressive phenotype of FLS and maintaining chondrocyte homeostasis in the context of RA. METHODS: The expression of Rspo2 in knee joint synovium and cartilage were detected in RA mice with antigen-induced arthritis (AIA) and RA patients. Recombinant mouse Rspo2 (rmRspo2), Rspo2 neutralizing antibody (Rspo2-NAb), and recombinant mouse DKK1 (rmDKK1, a potent inhibitor of Wnt signaling pathway) were used to explore the role and mechanism of Rspo2 in the progression of RA, specifically in relation to the aggressive phenotype of FLS and chondrocyte homeostasis, both in vivo and in vitro. RESULTS: We indicated that Rspo2 expression was upregulated both in synovium and articular cartilage as RA progressed in RA mice and RA patients. Increased Rspo2 upregulated the expression of leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), as the ligand for Rspo2, and ß-catenin in FLS and chondrocytes. Subsequent investigations revealed that intra-articular administration of rmRspo2 caused striking progressive synovitis and articular cartilage destruction to exacerbate RA progress in mice. Conversely, neutralization of Rspo2 or inhibition of the Wnt/ß-catenin pathway effectively alleviated experimental RA development. Moreover, Rspo2 facilitated FLS aggressive phenotype and disrupted chondrocyte homeostasis primarily through activating Wnt/ß-catenin pathway, which were effectively alleviated by Rspo2-NAb or rmDKK1. CONCLUSIONS: Our data confirmed a critical role of Rspo2 in enhancing the aggressive phenotype of FLS and disrupting chondrocyte homeostasis through the Wnt/ß-catenin pathway in the context of RA. Furthermore, the results indicated that intra-articular administration of Rspo2 neutralizing antibody or recombinant DKK1 might represent a promising therapeutic strategy for the treatment of RA.


Assuntos
Artrite Reumatoide , Cartilagem Articular , Sinoviócitos , Sinovite , Animais , Humanos , Camundongos , Anticorpos Neutralizantes/genética , Artrite Reumatoide/genética , beta Catenina/metabolismo , Cartilagem Articular/metabolismo , Proliferação de Células , Condrócitos/metabolismo , Fibroblastos/metabolismo , Homeostase , Fenótipo , Receptores Acoplados a Proteínas G/genética , Membrana Sinovial/metabolismo , Sinoviócitos/metabolismo , Via de Sinalização Wnt/genética
10.
Front Bioeng Biotechnol ; 11: 1184463, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37324445

RESUMO

The repair of bone defects resulting from high-energy trauma, infection, or pathological fracture remains a challenge in the field of medicine. The development of biomaterials involved in the metabolic regulation provides a promising solution to this problem and has emerged as a prominent research area in regenerative engineering. While recent research on cell metabolism has advanced our knowledge of metabolic regulation in bone regeneration, the extent to which materials affect intracellular metabolic remains unclear. This review provides a detailed discussion of the mechanisms of bone regeneration, an overview of metabolic regulation in bone regeneration in osteoblasts and biomaterials involved in the metabolic regulation for bone regeneration. Furthermore, it introduces how materials, such as promoting favorable physicochemical characteristics (e.g., bioactivity, appropriate porosity, and superior mechanical properties), incorporating external stimuli (e.g., photothermal, electrical, and magnetic stimulation), and delivering metabolic regulators (e.g., metal ions, bioactive molecules like drugs and peptides, and regulatory metabolites such as alpha ketoglutarate), can affect cell metabolism and lead to changes of cell state. Considering the growing interests in cell metabolic regulation, advanced materials have the potential to help a larger population in overcoming bone defects.

11.
Eur J Pharmacol ; 954: 175868, 2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37369296

RESUMO

Postmenopausal osteoporosis stems mainly from estrogen deficiency leading to a gut microbiome-dependent disruption of host systemic immunity. However, the underlying mechanisms of estrogen deficiency-induced bone loss remain elusive and novel pharmaceutical intervention strategies for osteoporosis are needed. Here we reveal that ovariectomy (ovx)-induced estrogen deficiency in C57BL/6 mice causes significant disruption of gut microbiota composition, consequently leading to marked destruction of intestinal barrier function and gut leakage. As a result, signals transportation between intestinal microbiota and T cells from the gut to bone marrow is identified to contribute to osteoclastogenesis in ovx mice. Notably, we show that icariside I (GH01), a novel small molecule naturally occurring in Herbal Epimedium, has potential to alleviate or prevent ovx-induced bone loss in mice through regulation of gut-bone signaling axis. We find that GH01 treatment can effectively restore the gut microbiota composition, intestinal barrier function and host immune status markedly altered in ovx mice, thus significantly ameliorating bone loss and osteoporosis. These findings not only provide systematic understanding of the gut-immunity-bone axis-associated pathophysiology of osteoporosis, but also demonstrate the high potential of GH01 for osteoporosis treatment by targeting the gut-bone signaling axis.


Assuntos
Osteoporose Pós-Menopausa , Osteoporose , Humanos , Feminino , Camundongos , Animais , Camundongos Endogâmicos C57BL , Osteoporose/tratamento farmacológico , Osteoporose/etiologia , Osteoporose/prevenção & controle , Osteoporose Pós-Menopausa/tratamento farmacológico , Osso e Ossos , Estrogênios , Ovariectomia
12.
Front Cell Dev Biol ; 11: 1131481, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37123405

RESUMO

Fibrotic ligament diseases (FLDs) are diseases caused by the pathological accumulation of periarticular fibrotic tissue, leading to functional disability around joint and poor life quality. Relaxin (RLX) has been reported to be involved in the development of fibrotic lung and liver diseases. Previous studies have shown that RLX can block pro-fibrotic process by reducing the excess extracellular matrix (ECM) formation and accelerating collagen degradation in vitro and in vivo. Recent studies have shown that RLX can attenuate connective tissue fibrosis by suppressing TGF-ß/Smads signaling pathways to inhibit the activation of myofibroblasts. However, the specific roles and mechanisms of RLX in FLDs remain unclear. Therefore, in this review, we confirmed the protective effect of RLX in FLDs and summarized its mechanism including cells, key cytokines and signaling pathways involved. In this article, we outline the potential therapeutic role of RLX and look forward to the application of RLX in the clinical translation of FLDs.

13.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 37(5): 556-560, 2023 May 15.
Artigo em Chinês | MEDLINE | ID: mdl-37190831

RESUMO

Objective: To testify the spatial relationship between the subscapularis muscle splitting window and the axillary nerve in modified arthroscopic Latarjet procedure, which could provide anatomical basis for the modification of the subscapularis muscle splitting. Methods: A total of 29 adult cadaveric shoulder specimens were dissected layer by layer, and the axillary nerve was finally confirmed to walk on the front surface of the subscapularis muscle. Keeping the shoulder joint in a neutral position, the Kirschner wire was passed through the subscapularis muscle from back to front at the 4 : 00 position of the right glenoid circle (7 : 00 position of the left glenoid circle), and the anterior exit point (point A, the point of splitting subscapularis muscle during Latarjet procedure) was recorded. The vertical and horizontal distances between point A and the axillary nerve were measured respectively. Results: In the neutral position of the shoulder joint, the distance between the point A and the axillary nerve was 27.37 (19.80, 34.55) mm in the horizontal plane and 16.67 (12.85, 20.35) mm in the vertical plane. Conclusion: In the neutral position of the shoulder joint, the possibility of axillary nerve injury will be relatively reduced when radiofrequency is taken from the 4 : 00 position of the right glenoid (7 : 00 position of the left glenoid circle), passing through the subscapularis muscle posteriorly and anteriorly and splitting outward.


Assuntos
Instabilidade Articular , Articulação do Ombro , Adulto , Humanos , Ombro , Manguito Rotador/cirurgia , Artroscopia/métodos , Escápula/cirurgia , Articulação do Ombro/cirurgia , Cadáver , Instabilidade Articular/cirurgia
14.
iScience ; 26(6): 106775, 2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37213227

RESUMO

The strategies for eliminating excess reactive oxygen species (ROS) or suppressing inflammatory responses on the wound bed have proven effective for diabetic wound healing. In this work, a zinc-based nanoscale metal-organic framework (NMOF) functions as a carrier to deliver natural product berberine (BR) to form BR@Zn-BTB nanoparticles, which was, in turn, further encapsulated by hydrogel with ROS scavenging ability to yield a composite system of BR@Zn-BTB/Gel (denoted as BZ-Gel). The results show that BZ-Gel exhibited the controlled release of Zn2+ and BR in simulated physiological media to efficiently eliminated ROS and inhibited inflammation and resulted in a promising antibacterial effect. In vivo experiments further proved that BZ-Gel significantly inhibited the inflammatory response and enhanced collagen deposition, as well as to re-epithelialize the skin wound to ultimately promote wound healing in diabetic mice. Our results indicate that the ROS-responsive hydrogel coupled with BR@Zn-BTB synergistically promotes diabetic wound healing.

15.
Adv Healthc Mater ; 12(20): e2300303, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36964976

RESUMO

Treatment of infected bone defects is a major clinical challenge; bioactive materials combining sufficient antimicrobial activity and favorable osteogenic ability are urgently needed. In this study, through a facile one-pot hydrothermal reaction of zinc acetate in the presence of tannic acid (TA), with or without silver nitrate (AgNO3 ), is used to synthesize a TA or TA and silver nanoparticles (Ag NPs) bulk-modified zinc oxide (ZnO) (ZnO-TA or ZnO-TA-Ag), which is further composited with zein to fabricate porous microparticulate scaffolds for infected bone defect repair. Bulk TA modification significantly improves the release rate of antibacterial metal ions (Zn2+ release rate is >100 times that of ZnO). Fast and long-lasting (>35 d) Zn2+ and Ag+ release guaranteed sufficient antibacterial capability and excellent osteogenic properties in promoting the osteogenic differentiation of bone marrow mesenchymal stem cells and endogenous citric acid production and mineralization and providing considerable immunomodulatory activity in promoting M2 polarization of macrophages. At the same time, synchronously-released TA could scavenge endogenous reactive oxygen species (ROS) and ROS produced by antibacterial metal ions, effectively balancing antibacterial activity and osteogenesis to sufficiently control infection while protecting the surrounding tissue from damage, thus effectively promoting infected bone defect repair.


Assuntos
Anti-Infecciosos , Nanopartículas Metálicas , Óxido de Zinco , Osteogênese , Zinco/farmacologia , Óxido de Zinco/farmacologia , Espécies Reativas de Oxigênio , Taninos/farmacologia , Prata/farmacologia , Antibacterianos/farmacologia , Íons/farmacologia , Anti-Infecciosos/farmacologia , Alicerces Teciduais
16.
ACS Pharmacol Transl Sci ; 6(2): 270-280, 2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36798476

RESUMO

Regulation of osteoblast-mediated bone formation and osteoclast-mediated bone resorption is crucial for bone health. Currently, most clinical drugs for osteoporosis treatment such as bisphosphonates are commonly used to inhibit bone resorption but unable to promote bone formation. In this study, we discovered for the first time that icariside I (GH01), a novel prenylflavonoid isolated from Epimedium, can effectively ameliorate estrogen deficiency-induced osteoporosis with enhancement of trabecular and cortical bone in an ovariectomy (OVX) mouse model. Mechanistically, our in vitro results showed that GH01 repressed osteoclast differentiation and resorption through inhibition of RANKL-induced TRAF6-MAPK-p38-NFATc1 cascade. Simultaneously, we also found that GH01 dose-dependently promoted osteoblast differentiation and formation by inhibiting adipogenesis and accelerating energy metabolism of osteoblasts. In addition, both in vitro and in vivo studies also suggested that GH01 is not only a non-toxic natural small molecule but also beneficial for restoration of liver injury in OVX mice. These results demonstrated that GH01 has great potential for osteoporosis treatment by simultaneous regulation of osteoblast and osteoclast differentiation.

17.
Front Cell Dev Biol ; 10: 971736, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36120586

RESUMO

Osteoarthritis (OA) is a progressive degenerative joint disease characterized by the destruction of the articular cartilage, meniscus and the like. Autophagy and cellular energy metabolism are the mechanisms by which cells maintain homeostasis. However, little is known about the effects of autophagy and cellular energy metabolism on meniscus degeneration, and the pathogenesis of posttraumatic osteoarthritis (PTOA) after the meniscal injury is rarely reported. Therefore, this study aimed to investigate the relationship between changes in autophagy and cellular energy metabolism in the meniscus following anterior cruciate ligament transection (ACLT) and PTOA induced by subsequent articular cartilage injury. In this study, we use a combination of cell experiments in vitro and animal experiments in vivo. On the one hand, cell experiment results show that inhibiting the mTORC1 signaling pathway by inhibiting the phosphorylation of S6K and AKT proteins in meniscal cells will lead to the increase of Beclin1, LC-3B, ATG12, ULK1, P62, and activate autophagy-related signaling pathways, which in turn protects the extracellular matrix component COL1 of meniscal cells from degradation by catabolic factor MMP13. In addition, it increased the generation of mitochondrial membrane potential in meniscal cells, increased the expression of anti-apoptotic factor BCL-XL, decreased the expression of pro-apoptotic factors BAD and BAX, and reduced the apoptosis of meniscal cells. More importantly, under the stimulation of inflammatory factor IL-1ß, the secretion of meniscus cells can reduce the elevated levels of MMP13 and Adamts5 caused by chondrocytes affected by IL-1ß. On the other hand, the results of animal experiments in vivo further proved the validity of the results of the cell experiments, and also proved that the meniscus injury did prior to the articular cartilage degeneration after ACLT. In conclusion, this study suggests that the meniscus prior to articular cartilage damage during the development of PTOA after ACLT, and that promoting autophagy and energy metabolism of meniscal cells may be a potential therapeutic target for delaying PTOA.

18.
J Clin Med ; 11(15)2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35956163

RESUMO

Hip arthroscopy is difficult to perform due to the limited arthroscopic view. To solve this problem, the capsulotomy is an important technique. However, the existing capsulotomy approaches were not perfect in the surgical practice. Thus, this study aimed to propose a modified longitudinal capsulotomy by outside-in approach and demonstrate its feasibility and efficacy in arthroscopic femoroplasty and acetabular labrum repair. A retrospective cohort study was performed and twenty-two postoperative patients who underwent hip arthroscopy in our hospital from January 2019 to December 2021 were involved in this study. The patients (14 females and 8 males) had a mean age of 38.26 ± 12.82 years old. All patients were diagnosed cam deformity and labrum tear in the operation and underwent arthroscopic femoroplasty and labrum repair by the modified longitudinal capsulotomy. The mean follow-up time was 10.4 months with a range of 6−12 months. There were no major complications, including infection, neurapraxias, hip instability or revision in any patients. The average mHHS were 74.4 ± 15.2, 78.2 ± 13.7 and 85.7 ± 14.5 in 3 months, 6 months and 12 months after surgery, respectively, which were all better than that before surgery (44.9 ± 8.6) (p < 0.05). The average VAS were 2.8 ± 1.2, 1.5 ± 0.6 and 1.2 ± 0.7 in 3 months, 6 months and 12 months after surgery, respectively, which were all lower than that before surgery (5.5 ± 2.0) (p < 0.05). The modified longitudinal capsulotomy by outside-in approach is proved to be a safe and feasible method for hip arthroscopy considering to the feasibility, efficacy and security. The arthroscopic femoroplasty and labrum repair can be performed conveniently by this approach and the patient reported outcomes after surgery were better that before surgery in short-term follow-up. This new method is promising and suggested to be widely used clinically.

19.
Bone Joint Res ; 11(7): 503-512, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35866455

RESUMO

AIMS: To verify whether secretory leucocyte protease inhibitor (SLPI) can promote early tendon-to-bone healing after anterior cruciate ligament (ACL) reconstruction. METHODS: In vitro: the mobility of the rat bone mesenchymal stem cells (BMSCs) treated with SLPI was evaluated by scratch assay. Then the expression levels of osteogenic differentiation-related genes were analyzed by real-time quantitative PCR (qPCR) to determine the osteogenic effect of SLPI on BMSCs. In vivo: a rat model of ACL reconstruction was used to verify the effect of SLPI on tendon-to-bone healing. All the animals of the SLPI group and the negative control (NC) group were euthanized for histological evaluation, micro-CT scanning, and biomechanical testing. RESULTS: SLPI improved the migration ability of BMSCs and upregulated the expression of genes related to osteogenic differentiation of BMSCs in vitro. In vivo, the SLPI group had higher histological scores at the tendon-bone interface by histological evaluation. Micro-CT showed more new bone formation and bone ingrowth around the grafted tendon in the SLPI group. Evaluation of the healing strength of the tendon-bone connection showed that the SLPI group had a higher maximum failure force and stiffness. CONCLUSION: SLPI can effectively promote early tendon-to-bone healing after ACL reconstruction via enhancing the migration and osteogenic differentiation of BMSCs. Cite this article: Bone Joint Res 2022;11(7):503-512.

20.
Transl Pediatr ; 11(5): 687-695, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35685077

RESUMO

Background: Derotational osteotomy remains the most commonly performed procedure in patients with congenital radioulnar synostosis (CRUS). Bone fixation is mostly performed using K-wires or plates. Many scars, loss of correction and neurovascular complications in the form were the most common complications across the studies. This report introduces a novel, minimally-invasive surgical approach, and reviews our experience. Methods: Twenty-seven children with CRUS were treated using the new technique, including bilateral forearms in 12 cases and unilateral forearm in 15 cases. A transverse osteotomy was performed at the ulnar and radial fusion site, the forearm was derotated osteotomy to the target position, intramedullary nailing was performed, and the elbow was flexed 90 degrees with a long-arm cast after surgery. One week after surgery, the forearm swelling disappeared, the long-arm cast was replaced, the elbow flexed at 90 degrees, and the forearm fixed in the maximum supination position for 4 weeks. Pre- and post-operative positions of the forearm were recorded; the pre- and post-operative activities of daily living (ADL) item scores were recorded for each patient. Results: All patients were followed up postoperatively for a mean duration of 20.7 months. The mean initial pronation deformity was 59.7±12.20 (40 to 100) degrees. The mean correction achieved was 51.2±14.50 degrees, resulting in a mean final position of 8.59±8.10 degrees of supination. The fixed angles of forearm pronation after surgery were corrected to 0-20°, with a mean of 8.33º [standard deviation (SD) 7.98°), and the difference was statistically significant compared with that before surgery (P<0.01). The patients' pre- and post-operative ADL item scores were 3.6 and 4.5, respectively, which was a 0.9-point change and was statistically significant (P<0.01). After surgery, 26 patients obtained good healing, and only one patient had delayed union, which was healed with forearm immobilization for a further month. Conclusions: Rotational osteotomy with single incision and elastic fixation for CRUS in children is a simple operation, and provides advantages including small trauma, fewer postoperative complications, and good efficacy.

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