Superior approach to the glenoid for treating acromion fractures combined with ideberg type III scapular glenoid fractures: a technical note.

PURPOSE: Scapular glenoid fractures, categorized based on the Ideberg classification, are commonly addressed surgically through approaches like the anterior deltoid-pectoral approach, posterior Judet approach, modified Judet approach, or posterior axillary approach. However, these methods present limitations in exposing the superior part of the glenoid. Therefore, we propose an approach for patients with concomitant acromion fractures, involving the anterior lateral flipping of the fractured acromion, allowing direct superior visualization of the superior and posterior superior parts of the glenoid. METHOD: Retrospective analysis was conducted on the data of five patients with shoulder fractures combined with scapular Ideberg III fractures between June 2018 and May 2023. All patients were treated using the shoulder approach above the scapular spine. There were four males and one female, aged 23-54 years with an average age of 36.6 years. One case involved the left shoulder, and four cases involved the right shoulder. X-rays and CT were taken before and after surgery to assess the location of the fractures and the healing status. Clinical evaluation included the assessment of efficacy using the Constant-Murley scoring criteria and analysis of surgical complications. RESULTS: All five patients were followed up for a duration of 14-36 months. All fractures healed completely, with an average healing time of 4.3 months (range: 3-6 months). There were no complications such as suprascapular nerve injury, nonunion, wound infection, or shoulder joint instability observed postoperatively. At the final follow-up, the Constant-Murley shoulder joint function score ranged from 84 to 98 points, with an average of 91.4 points. Three patients achieved an excellent rating in shoulder joint function score, while two patients achieved a good rating. CONCLUSION: The shoulder approach above the scapular spine exhibits advantages such as easy exposure and reduction, minimal intraoperative trauma, and clear visualization.

Umbilical cord mesenchymal stem cells relieve osteoarthritis in rats through immunoregulation and inhibition of chondrocyte apoptosis.

This study aims to investigate the effectiveness of umbilical cord mesenchymal stem cells (UCMSCs) in treating osteoarthritis (OA). Sprague-Dawley rats were used in in vivo experiments and divided into four groups: normal, OA model, saline, and UCMSC-treated groups (n = 6). An OA model was established by injecting iodoacetic acid into the joint cavity. The results indicate that UCMSC transplantation significantly reduced joint surface and articular cartilage damage, and the levels of IL-1ß, TNF-α, and MMP13 in the joint fluid were significantly reduced after UCMSC treatment. In vitro experiments showed that co-culturing UCMSCs and chondrocytes promoted the expression of aggrecan, COL2, SOX9, and BCL-2; downregulated the expression of BAX and BAD in chondrocytes; and promoted the expression of IL-10 and TGF-ß1 in UCMSCs. Additionally, the supernatant of UCMSCs inhibited the expression of IL-1ß and TNF-α in the articular cavity and promoted the expression of COL2 and aggrecan in vivo. These effects were impaired when IL-10 and TGF-ß1 were removed. Collectively, UCMSC transplantation appears to improve joint pathology, reduce inflammatory factors, and decrease chondrocyte apoptosis, likely through the involvement of IL-10 and TGF-ß1, thus providing a potential therapeutic option for patients with OA.

Strategy insight: Mechanical properties of biomaterials' influence on hydrogel-mesenchymal stromal cell combination for osteoarthritis therapy.

Osteoarthritis (OA) is a kind of degenerative joint disease usually found in older adults and those who have received meniscal surgery, bringing great suffering to a number of patients worldwide. One of the major pathological features of OA is retrograde changes in the articular cartilage. Mesenchymal stromal cells (MSCs) can differentiate into chondrocytes and promote cartilage regeneration, thus having great potential for the treatment of osteoarthritis. However, improving the therapeutic effect of MSCs in the joint cavity is still an open problem. Hydrogel made of different biomaterials has been recognized as an ideal carrier for MSCs in recent years. This review focuses on the influence of the mechanical properties of hydrogels on the efficacy of MSCs in OA treatment and compares artificial materials with articular cartilage, hoping to provide a reference for further development of modified hydrogels to improve the therapeutic effect of MSCs.

Melatonin prevents the binding of vascular endothelial growth factor to its receptor and promotes the expression of extracellular matrix-associated genes in nucleus pulposus cells.

The mechanisms of intervertebral disc degeneration (IDD) involve numerous factors, including loss of the extracellular matrix (ECM) and vascular ingrowth. Melatonin has been reported to protect intervertebral discs (IVDs) from degeneration and to exert a potential anti-angiogenic effect. The aim of the present study was to investigate the anti-angiogenic and anabolic effects of melatonin in IVDs. Human nucleus pulposus (NP) and degenerative nucleus pulposus (DNP) cells were isolated and treated with melatonin. The results indicated that melatonin promoted ECM synthesis and NP cell proliferation. In addition, an NP/DNP and human umbilical vein endothelial cell (HUVEC) co-culture model was used to investigate the anti-angiogenesis effect of melatonin. Melatonin was indicated to suppress tube formation and migration of HUVECs in culture with NP cell-conditioned medium, as well as in an NP cell co-culture model. Fluorescence-labeled vascular endothelial growth factor (VEGF) was used to study the binding between VEGF and its receptor. The results of the present study indicated that melatonin exerts an angiogenic effect via inhibition of the binding of VEGF to its receptor in HUVECs. Taken together, these results suggest that melatonin is a potential agent to prevent IDD.

[Treatment of proximal humeral fractures with proximal humeral locking system plate via an intertubercular sulcus approach].

OBJECTIVE: To observe the effect of proximal humerus internal locking system (PHILOS) plate in the treatment of Neer 2 and 3 part fractures of proximal humerus through tuberosity approach. METHODS: From July 2015 to January 2018, 15 cases of proximal humerus Neer 2 and 3 fractures were treated with PHILOS plate through intertubercular sulcus approach. There were 7 males and 8 females. The age ranged from 23 to 67 years old, with an average of 46 years old. There were 5 cases on the left side and 10 cases on the right side (including 7 cases of Neer 2 partial fracture and 8 cases of Neer 3 partial fracture). X-ray films and CT were taken before and after operation to assess fracture location and fracture healing. Clinical evaluation included Constant-Murley shoulder function score and operative complications. All 15 patients were treated with the PHILOS. Constant-Murley score was used to evaluate shoulder function after operation. RESULTS: All the 15 cases were followed up, and the duration ranged from 14 to 36 months. All the fractures healed and the healing time ranged from 14 to 26 weeks, averaged 19.1 weeks. There were no complications such as humeral head necrosis, axillary nerve injury and fracture nonunion after operation. At the 3rd month after operation, the shoulder function score of Constant-Murley ranged from 72 to 94 points, with an average of 81 points; 2 cases got an excellent result and 13 good. CONCLUSIONS: The PHILOS plate for the treatment of proximal humerus fractures has the advantages of simple operation, small injury and quick recovery of shoulder joint function.

Silencing of Barkor/ATG14 sensitizes osteosarcoma cells to cisplatin­induced apoptosis.

Although surgical excision following neoadjuvant chemotherapy has contributed to the long-term survival of osteosarcoma patients, patients that do not respond to commonly used drugs including cisplatin, have a poor prognosis. Autophagy is important in the inhibition of chemotherapeutic apoptosis. Therefore, we investigated whether knockdown of Beclin1-associated autophagy-related key regulator (Barkor/ATG14) promoted cisplatin-induced apoptosis in a drug-resistant osteosarcoma cell line in vitro. Saos-2 cells were transfected with Barkor siRNA. Sensitivity of the Barkor siRNA-transfected cell line to cisplatin was evaluated. Silencing of Barkor did not directly inhibit the growth rate of the transfected cells, but it significantly increased their sensitivity to cisplatin. The results of flow cytometry and 4',6-diamidino-2-phenylindole (DAPI) staining revealed that Barkor siRNA-transfected Saos-2 cells treated with cisplatin exhibited much higher rates of apoptosis than the control and control siRNA-transfected cells. Additionally, the combination of silencing of Barkor with cisplatin treatment promoted the expression of caspase-12 and calpain. The increase of cisplatin cytotoxicity may therefore be involved in endoplasmic reticulum (ER) stress-associated apoptosis. Bcl-2 was markedly downregulated in dose­dependent cisplatin­treated Barkor-transfected-Saos-2 cells. Findings of the present study suggest that the combination of silencing of Barkor and cisplatin enhanced the antitumor efficacy through the Barkor­related ER- and mitochondrial-mediated apoptotic pathway.

Tetrandrine induces apoptosis and triggers a caspase cascade in U2-OS and MG-63 cells through the intrinsic and extrinsic pathways.

Although neoadjuvant chemotherapy has improved the survival rate of osteosarcoma patients, drug resistance remains a predominant obstacle to improving efficacy and necessitates the development of novel chemotherapeutical agents. The aim of this study was to investigate whether tetrandrine (TET) induces apoptosis in the U-2OS and MG-63 osteosarcoma cell lines and to further determine the underlying mechanism. This study investigated the effects of TET on osteosarcoma in vitro. To examine the antitumor effects of TET on osteosarcoma, the two osteosarcoma cell lines were treated with TET and subjected to apoptosis assays. The results revealed that TET induced the apoptosis of osteosarcoma cells in a time- and dose-dependent manner. Furthermore, the apoptosis of osteosarcoma cells was accompanied by increased cytochrome c (Cyto-C), apoptotic protease-activating factor (Apaf)-1, Bid and Bax activation and reduced Bcl-2 and Bcl-xl activation, demonstrating that the apoptosis may have occurred through the mitochondrial pathway. In conclusion, the results suggest that TET is a promising agent for osteosarcoma therapy.

Chloroquine blocks the autophagic process in cisplatin-resistant osteosarcoma cells by regulating the expression of p62/SQSTM1.

Cisplatin (DDP) is one of the most effective chemotherapeutic drugs against osteosarcoma (OS), the most common malignant bone-specific tumor. However, the acquired resistance to DDP limits its effectiveness in tumor treatment. In this study, in order to elucidate the mechanisms of drug resistance in cancer cells, we investigated cell death induced by DDP in OS cells. We evaluated the contribution of autophagy in the process of drug resistance in a panel of four OS cell lines, MG-63, U-2OS, MNNG/HOS and Saos-2. The cells were treated with DDP (0-50 µM) for 48 h and then cell vaibility was assessed using the Cell Counting kit-8 (CCK-8). Apoptosis was detected by flow cytometry and the green fluorescent protein (GFP)-microtubule-associated protein 1 light chain 3 (LC3) expression vector was used to visualize the formation of autophagic vesicles. Our results demonstrated that autophagy was induced by DDP in the drug-resistant cell line, Saos-2, which does not respond to DDP with apoptosis. DDP-induced autophagy protected the Saos-2 cells from apoptotic cell death. Moreover, the inhibition of autophagy by chloroquine, an inhibitor of lysosomal proteases, accelerated the DDP-induced cell death in Saos-2 cells. We also found that during DDP treatment, the protein expression level of the autophagic regulator, p62/sequestosome 1 (SQSTM1), decreased during the first hour of treatment, followed by a rapid recovery. Therefore, our data suggest a potential clinical therapy by targeting autophagy with chloroquine or monoclonal antibodies for the treatment of drug-resistant OS.

Gambogic acid inhibits invasion of osteosarcoma via upregulation of TIMP-1.

Gambogic acid (GA), the natural product, has been demonstrated to be a promising chemotherapeutic drug for osteosarcoma (OS) due to its ability to induce apoptosis and cell cycle arrest. To date, no studies have examined the role of GA in metastatic bone disease. Matrix metalloproteinases (MMPs) play critical roles in invasion and metastasis, and the tissue inhibitors of metalloproteinase (TIMP) family regulates the activity of multifunctional metalloproteinases. In this study, we investigated the gene expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in OS cell lines treated by the GA. The expression of MMP-9 and TIMP-1 were studied by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting. In vitro invasion of OS cell lines (Saos-2, MG-63) were investigated by the Matrigel invasion assay. Mean MMP-9 protein and mRNA expression was significantly suppressed; in addition, mean TIMP-1 protein mRNA expression were upregulated by increasing GA concentrations. GA reduced the invasiveness of OS cell lines dose-dependently. Furthermore, specific inhibition of TIMP-1 secretion with siRNA against TIMP-1 significantly reduced the effect of GA on OS cell lines. Overall, our findings suggest that GA reduces the invasive potential of OS cells via attenuation of MMP-9 and upregulation of TIMP-1. Moreover, TIMP-1 played an important role in the reduction of invasive potential of the OS cells which were treated by GA.

Elevated local TGF-ß1 level predisposes a closed bone fracture to tuberculosis infection.

Tuberculosis (TB) occurring after a closed bone fracture in the patient with no history of TB and no evidence of TB infection at the time of initial fracture is a rare entity. Transforming growth factor-beta 1 (TGF-ß1) is a ubiquitous growth factor that is implicated in the regulation of the proliferation, differentiation, migration, and survival of many different cell types. Recent studies have demonstrated that the local level of TGF-ß1 in bone is significantly elevated during fracture healing and TGF-ß1 plays an important role in TB progression. Given the above background, we hypothesize that elevated local TGF-ß1 level predisposes a closed bone fracture to TB infection. This was supported by conclusions drawn from literature reviews: (1) the local level of TGF-ß1 in bone is significantly elevated during fracture healing; (2) TGF-ß1 inhibits T lymphocyte activation; (3) TGF-ß1 is a potent macrophage-deactivating molecule; (4) TGF-ß1 suppresses the production and activity of some proinflammatory cytokines.

Genistein potentiates the anti-cancer effects of gemcitabine in human osteosarcoma via the downregulation of Akt and nuclear factor-κB pathway.

Genistein, a nontoxic flavonoid compound, has potent antitumor activity in various cancer cells. In the present study, we investigated whether genistein could be employed as a novel strategy to enhance the anti-tumor activity of gemcitabine using human osteosarcoma MNNG/HOS tumor model. In vitro, by MTT, electron microscopy, immunobloting and qRT-PCR assay, we found that the combination treatment of genistein and gemcitabine resulted in stronger growth inhibition and apoptosis induction through the downregulation of NF-κB activity and Akt activation in osteosarcoma cells. Moreover, the synergetic effects were observed when genistein was replaced by PI3K/Akt-pathway inhibitor (LY-294002) or NF-κB inhibitor (BAY11-7082). In vivo, the combination therapy augmented tumor growth inhibition through the down-regulation of NF-κB activity and Akt activation in xenografts. Taken together, these results provide in vitro and in vivo evidence that genistein abrogates gemcitabine-induced activation of NF-κB and increases the chemosensitization of osteosarcoma to gemcitabine. Combination therapy appears as a rational and novel approach for osteosarcoma treatment.

Matrine induces caspase-dependent apoptosis in human osteosarcoma cells in vitro and in vivo through the upregulation of Bax and Fas/FasL and downregulation of Bcl-2.

PURPOSE: Matrine, one of the main active components of extracts from the dry roots of Sophora flavescens, has potent anti-tumor activity in various cancer cell lines. However, the activity of matrine against osteosarcoma remains unclear. In the present study, we examined the effects of matrine on human osteosarcoma cells and explored the underlying mechanism. METHODS: Four human osteosarcoma cell lines: MG-63, U-2OS, Saos-2, and MNNG/HOS were treated by matrine and subjected to MTT assay, annexin V-FITC/PI double staining, and TUNEL assay. The activation of caspases and the expression of pro-apoptotic and anti-apoptotic factors were examined by qRT-PCR and Western blot. In addition, MNNG/HOS xenograft tumors were established in female nude BALB/c mice, and matrine was intraperitoneally (i.p.) administered to evaluate the anti-cancer capacity of matrine in vivo. RESULTS: We found that matrine inhibited the proliferation and induced apoptosis of the four osteosarcoma cell lines in vitro and induced the activation of caspase-3, -8, and -9 in a dose-dependent manner. Furthermore, the pro-apoptotic factors Bax and Fas/FasL were upregulated, and the anti-apoptotic Bcl-2 was downregulated. More importantly our in vivo, studies showed that administration of matrine decreased tumor growth in a dose-dependent manner. Immunohistochemistry analysis demonstrated the downregulation of Bcl-2 and upregulation of Bax and Fas/FasL in MNNG/HOS tumor tissues following matrine treatment, consistent with the in vitro results. CONCLUSION: Our results demonstrate that matrine inhibits the proliferation and induces apoptosis of human osteosarcoma cells in vitro and in vivo. The induction of apoptosis appears to occur through the upregulation of Fas/FasL and Bax, downregulation of Bcl-2, and activation of caspase-3, -8, and -9, which then trigger major apoptotic cascades.

Decreases in fluid shear stress due to microcracks: a possible primary pathogenesis of Kümmell's disease.

The German doctor Hermann Kümmell described Kümmell's disease as the clinical scenario in which patients suffer a trivial spinal trauma, but develop a symptomatic, progressive, angular kyphosis after a symptom-free period of months to years. Since an intravertebral vacuum phenomenon, which is considered indicative of ischemic osteonecrosis, is often seen in the radiographs of patients with Kümmell's disease, most authors regard ischemic necrosis of the vertebral body as the primary pathogenesis of Kümmell's disease. However, we argue that Kümmell's disease is not commonly associated with typical avascular osteonecrosis of the femoral head and the intravertebral vacuum phenomenon is also present in other diseases. We postulated that even if ischemia plays a role in the pathogenesis of Kümmell's disease, it would not be the proximal cause of Kümmell's disease. In this article, we review the role of fluid shear stress in bone remolding and propose a microcosmic hypothesis in which microcracks lead to decreased fluid shear stress, which acts as the primary cause of Kümmell's disease. This was supported by conclusions drawn from a literature review: (1) fluid shear stress plays a crucial role in bone remodeling, and the osteocyte network is the main sensor of this mechanical stimulus; (2) decreased fluid shear stress will cause disequilibration of bone homeostasis, increasing bone resorption and reducing bone formation; and (3) the fluid flow of lacunar-canalicular porosity (PLC) and fluid shear stress near the microcracks decreases.