RESUMO
This study aimed to explore how mechanical stress affects osteogenic differentiation via the miR-187-3p/CNR2 pathway. To conduct this study, 24 female C57BL/6 mice, aged 8 weeks, were used and divided into four groups. The Sham and OVX groups did not undergo treadmill exercise, while the Sham + EX and OVX + EX groups received a 8-week treadmill exercise. Post-training, bone marrow and fresh femur samples were collected for further analysis. Molecular biology analysis, histomorphology analysis, and micro-CT analysis were conducted on these samples. Moreover, primary osteoblasts were cultured under osteogenic conditions and divided into GM group and CTS group. The cells in the CTS group underwent a sinusoidal stretching regimen for either 3 or 7 days. The expression of early osteoblast markers (Runx2, OPN, and ALP) was measured to assess differentiation. The study findings revealed that mechanical stress has a regulatory impact on osteoblast differentiation. The expression of miR-187-3p was observed to decrease, facilitating osteogenic differentiation, while the expression of CNR2 increased significantly. These observations suggest that mechanical stress, miR-187-3p, and CNR2 play crucial roles in regulating osteogenic differentiation. Both in vivo and in vitro experiments have confirmed that mechanical stress downregulates miR-187-3p and upregulates CNR2, which leads to the restoration of distal femoral bone mass and enhancement of osteoblast differentiation. Therefore, mechanical stress promotes osteoblasts, resulting in improved osteoporosis through the miR-187-3p/CNR2 signaling pathway. These findings have broad prospect and provide molecular biology guidance for the basic research and clinical application of exercise in the prevention and treatment of PMOP.
Assuntos
Diferenciação Celular , MicroRNAs , Osteoblastos , Osteogênese , Osteoporose Pós-Menopausa , Estresse Mecânico , Animais , Feminino , Humanos , Camundongos , Células Cultivadas , Camundongos Endogâmicos C57BL , MicroRNAs/genética , MicroRNAs/metabolismo , Osteoblastos/metabolismo , Osteoporose Pós-Menopausa/metabolismo , Osteoporose Pós-Menopausa/terapia , Osteoporose Pós-Menopausa/genética , Osteoporose Pós-Menopausa/patologia , Transdução de SinaisRESUMO
BACKGROUND: Two types of suture anchor insertion pathways (anterolateral portal vs lateral accessory portal) are used in arthroscopic anterior talofibular ligament (ATFL) repair. However, it is not clear which one is the better choice. This study aims to compare the clinical outcomes of these 2 suture anchor insertion pathways when performing arthroscopic ATFL lasso-loop repair for the treatment of chronic lateral ankle instability (CLAI). METHODS: From 2019 to 2021, patients with CLAI who underwent arthroscopic ATFL lasso-loop repair were retrospectively reviewed and divided into the anterolateral portal (ALP) group and the lateral accessory portal (LAP) group. A 1:1 propensity score matching was used to control confounding factors based on age, sex, body mass index, follow-up duration, preoperative visual analog scale (VAS) score, and Tegner score (ALP group, n = 26; LAP group, n = 26). Karlsson score, VAS score, Tegner score, operation time, anterior drawer test results, patient symptoms, and magnetic resonance (MR) evaluation of ATFL quality were used to describe the outcomes. RESULTS: The patient characteristics and follow-up durations were similar between the 2 groups. After a mean follow-up duration of 28.8 ± 2.3 months, the ALP group had significantly better Karlsson score, VAS score, and Tegner score improvement than the LAP group, with fewer symptoms. Seven patients in the LAP group still had a feeling of ankle instability, and 3 of them exhibited ankle laxity. CONCLUSION: In this study, we found that inserting the suture anchor through the anterolateral portal was associated with better outcomes compared to that through the lateral accessory portal when performing arthroscopic ATFL lasso-loop repair for CLAI patients. The improvement was greater for pain relief and function and was associated with a lower frequency of subjective ankle instability.
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Extracellular matrix (ECM) stiffening is a typical characteristic of cartilage aging, which is a quintessential feature of knee osteoarthritis (KOA). However, little is known about how ECM stiffening affects chondrocytes and other molecules downstream. This study mimicked the physiological and pathological stiffness of human cartilage using polydimethylsiloxane (PDMS) substrates. It demonstrated that epigenetic Parkin regulation by histone deacetylase 3 (HDAC3) represents a new mechanosensitive mechanism by which the stiffness matrix affected chondrocyte physiology. We found that ECM stiffening accelerated cultured chondrocyte senescence in vitro, while the stiffness ECM downregulated HDAC3, prompting Parkin acetylation to activate excessive mitophagy and accelerating chondrocyte senescence and osteoarthritis (OA) in mice. Contrarily, intra-articular injection with an HDAC3-expressing adeno-associated virus restored the young phenotype of the aged chondrocytes stimulated by ECM stiffening and alleviated OA in mice. The findings indicated that changes in the mechanical ECM properties initiated pathogenic mechanotransduction signals, promoted the Parkin acetylation and hyperactivated mitophagy, and damaged chondrocyte health. These results may provide new insights into chondrocyte regulation by the mechanical properties of ECM, suggesting that the modification of the physical ECM properties may be a potential OA treatment strategy.
Assuntos
Senescência Celular , Condrócitos , Regulação para Baixo , Matriz Extracelular , Histona Desacetilases , Osteoartrite , Animais , Condrócitos/metabolismo , Condrócitos/patologia , Histona Desacetilases/metabolismo , Histona Desacetilases/genética , Matriz Extracelular/metabolismo , Osteoartrite/patologia , Humanos , Camundongos , Senescência Celular/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Mitofagia/efeitos dos fármacos , Masculino , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Acetilação , Células CultivadasRESUMO
BACKGROUND: Whether arthroscopic microfracture is effective in treating cystic osteochondral lesions of the talus (OLTs) remains controversial. In this study, outcome parameters in patients with small and shallow subchondral cysts are compared to patients without cysts with the hypothesis that equivalent outcomes may be found after primary microfracture treatment. METHODS: From 2018 to 2021, all 50 OLTs treated with arthroscopic microfracture in the authors' hospital were retrospectively reviewed for eligibility. Single unilateral symptomatic lesions were included and divided into the cyst and noncyst groups, whereas kissing lesions and arthritic lesions were excluded. Numeric rating scale (NRS) scores, American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot scores, Tegner activity level scores, Foot and Ankle Ability Measure (FAAM) scores, and magnetic resonance (MR) imaging results were used to describe outcomes. RESULTS: A total of 35 patients were included, 16 in the cyst group and 19 in the noncyst group. The patient characteristics were similar between the 2 groups (P > .05). In the cyst group the average cysts depth was 5.0 ± 1.3 mm. After a mean follow-up duration of 36.2 ± 10.2 months, no significant differences were found between the 2 groups in NRS, AOFAS, FAAM, or Tegner score improvement (P > .05). Three patients (19%) in the cyst group had no NRS score improvement. CONCLUSION: OLTs with small and shallow subchondral cysts can be treated with arthroscopic microfracture and achieve similar outcomes as noncystic lesions. A few cystic lesions may not respond to microfracture treatment. LEVEL OF EVIDENCE: Level III, retrospective comparative study.
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Artroscopia , Cistos Ósseos , Tálus , Humanos , Tálus/cirurgia , Tálus/lesões , Estudos Retrospectivos , Feminino , Artroscopia/métodos , Adulto , Masculino , Cistos Ósseos/cirurgia , Cistos Ósseos/diagnóstico por imagem , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética , Artroplastia Subcondral/métodos , Cartilagem Articular/cirurgia , Cartilagem Articular/lesõesRESUMO
Reconstructing extensive cranial defects represents a persistent clinical challenge. Here, we reported a hybrid three-dimensional (3D) printed scaffold with modification of QK peptide and KP peptide for effectively promoting endogenous cranial bone regeneration. The hybrid 3D printed scaffold consists of vertically aligned cryogel fibers that guide and promote cell penetration into the defect area in the early stages of bone repair. Then, the conjugated QK peptide and KP peptide further regulate the function of the recruited cells to promote vascularization and osteogenic differentiation in the defect area. The regenerated bone volume and surface coverage of the dual peptide-modified hybrid scaffold were significantly higher than the positive control group. In addition, the dual peptide-modified hybrid scaffold demonstrated sustained enhancement of bone regeneration and avoidance of bone resorption compared to the collagen sponge group. We expect that the design of dual peptide-modified hybrid scaffold will provide a promising strategy for bone regeneration.
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Osteogênese , Alicerces Teciduais , Criogéis , Regeneração Óssea/fisiologia , Peptídeos , Impressão TridimensionalRESUMO
There has been increasing application of autologous costal chondral/osteochondral transplantation (ACCT/ACOT) and costa-derived chondrocyte implantation (ACCI) for articular cartilage repair over the past three decades. This review presents the major evidence on the properties of costal cartilage and bone and their qualifications as grafts for articular cartilage repair, the major clinical applications, and the risks and strategies for costal chondral/osteochondral graft(s) harvest. First, costal cartilage has many specific properties that help restore the articular surface. Costa, which can provide abundant cartilage and cylindrical corticocancellous bone, preserves permanent chondrocyte and is the largest source of hyaline cartilage. Second, in the past three decades, autologous costal cartilage-derived grafts, including cartilage, osteochondral graft(s), and chondrocyte, have expanded their indications in trauma and orthopaedic therapy from small to large joints, from the upper to lower limbs, and from non-weight-bearing to weight-bearing joints. Third, the rate of donor-site complications of ACCT or ACOT is low, acceptable, and controllable, and some skills and accumulated experience can help reduce the risks of ACCT and ACOT. Costal cartilage-derived autografting is a promising technique and could be an ideal option for articular chondral lesions with or without subchondral cysts. More high-quality clinical studies are urgently needed to help us further understand the clinical value of such technologies.
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Cartilagem Articular , Cartilagem Costal , Procedimentos Ortopédicos , Humanos , Cartilagem Articular/cirurgia , Cartilagem Articular/lesões , Condrócitos/transplante , Transplante AutólogoRESUMO
Critical-sized segmental long bone defects represent a challenging clinical dilemma in the management of battlefield and trauma-related injuries. The residual bone marrow cavity of damaged long bones contains many bone marrow mesenchymal stem cells (BMSCs), which provide a substantial source of cells for bone repair. Thus, a three-dimensional (3D) vertically aligned nanofiber scaffold (VAS) is developed with long channels and large pore size. The pore of VAS toward the bone marrow cavity after transplantation, enables the scaffolds to recruit BMSCs from the bone marrow cavity to the defect area. In vivo, it is found that VAS can significantly shorten gap distance and promote new bone formation compared to the control and collagen groups after 4 and 8 weeks of implantation. The single-cell sequencing results discovered that the 3D nanotopography of VAS can promote BMSCs differentiation to chondrocytes and osteoblasts, and up-regulate related gene expression, resulting in enhancing the activities of bone regeneration, endochondral ossification, bone trabecula formation, bone mineralization, maturation, and remodeling. The Alcian blue and bone morphogenetic protein 2 (BMP-2) immunohistochemical staining verified significant cartilage formation and bone formation in the VAS group, corresponding to the single-cell sequencing results. The study can inspire the design of next-generation scaffolds for effective long-bone regeneration is expected by the authors.
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Regeneração Óssea , Diferenciação Celular , Condrogênese , Células-Tronco Mesenquimais , Nanofibras , Osteogênese , Alicerces Teciduais , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Nanofibras/química , Alicerces Teciduais/química , AnimaisRESUMO
BACKGROUND: The authors developed a simple extensible external fixator, which has the advantages of easy application and inexpensiveness. The present study aimed to make a comparison between this external fixator and calcaneal traction in preoperative temporary fixation for malaligned ankle fractures and pilon fractures. METHODS: From May 2020 to February 2022, patients with malaligned ankle fractures or Rüedi-Allgöwer type 2 or 3 pilon fractures with obvious soft tissue swelling were retrospectively reviewed and divided into the calcaneal traction group and the external fixation group. The two groups of patients were matched 1:1 before making comparisons. RESULTS: A total of 38 patients were included. Higher General Comfort Questionnaire score and lower visual analog scale score were noticed in the external fixation group during hospitalization (p < 0.05), while the operation latency time, total cost, patient satisfaction, and functional outcomes one year after surgery were not significantly different between the two groups. No wound complications were observed. CONCLUSION: Preoperative temporary fixation for fractures around the ankle using this simple extensible external fixator significantly improves patient comfort when compared to calcaneal traction. LEVEL OF EVIDENCE: III, retrospective comparative study.