The effect of BMI on the mid-term clinical outcomes of mobile-bearing unicompartmental knee arthroplasty.

OBJECTIVE: To evaluate the impact of body mass index (BMI) on the mid-term clinical outcomes and survival in patients receiving a mobile-bearing unicompartmental knee arthroplasty (UKA). METHODS: We retrospectively collected data from 355 patients who underwent UKA from June 2006 to June 2015, with a mean follow-up of 106.5 ± 22.5 months. Patients were assigned into four groups based on their BMI before surgery: normal weight group (BMI 18.5 ~ 22.9 kg/m2), overweight group (23 ~ 24.9 kg/m2), obesity group (25 ~ 29.9 kg/m2), and severe obesity group (≥ 30 kg/m2). The knee society score (KSS), knee society function score (KSFS), hospital for special surgery score (HSS), and range of motion (ROM) were assessed before the operation and at the last follow-up. The femorotibial angle (FTA) was assessed after the operation immediately and at the last follow-up. Kaplan-Meier survival analysis was performed among the four groups. RESULTS: The KSS, KSFS, and HSS in all groups were markedly improved compared with the preoperative values (p<0.001), but the ROM score was not significantly different (p>0.05). There were significant differences in KSS (p<0.001) and HSS (p = 0.004) across the four BMI groups, and these differences were due to the severe obesity group. All groups exhibited an inclination of knee varus deformity at the last follow-up (p < 0.05). Moreover, no marked difference in the implant survival rate was found among the different groups (p = 0.248), or in the survival curves (p = 0.593). CONCLUSIONS: BMI does not influence the implant survival rate. The postoperative functional and quality-of-life scores were significantly improved in all groups. Obese (BMI ≥30 kg/m2) individuals should not be excluded from UKA.

G protein coupled estrogen receptor attenuates mechanical stress-mediated apoptosis of chondrocyte in osteoarthritis via suppression of Piezo1.

BACKGROUND: Apoptosis of chondrocyte is involved in osteoarthritis (OA) pathogenesis, and mechanical stress plays a key role in this process by activation of Piezo1. However, the negative regulation of signal conduction mediated by mechanical stress is still unclear. Here, we elucidate that the critical role of G protein coupled estrogen receptor (GPER) in the regulation of mechanical stress-mediated signal transduction and chondrocyte apoptosis. METHODS: The gene expression profile was detected by gene chip upon silencing Piezo1. The expression of GPER in cartilage tissue taken from the clinical patients was detected by RT-PCR and Western blot as well as immunohistochemistry, and the correlation between GPER expression and OA was also investigated. The chondrocytes exposed to mechanical stress were treated with estrogen, G-1, G15, GPER-siRNA and YAP (Yes-associated protein)-siRNA. The cell viability of chondrocytes was measured. The expression of polymerized actin and Piezo1 as well as the subcellular localization of YAP was observed under laser confocal microscope. Western blot confirmed the changes of YAP/ Rho GTPase activating protein 29 (ARHGAP29) /RhoA/LIMK /Cofilin pathway. The knee specimens of osteoarthritis model were stained with safranin and green. OARSI score was used to evaluate the joint lesions. The expressions of GPER and YAP were detected by immunochemistry. RESULTS: Expression profiles of Piezo1- silenced chondrocytes showed that GPER expression was significantly upregulated. Moreover, GPER was negatively correlated with cartilage degeneration during OA pathogenesis. In addition, we uncovered that GPER directly targeted YAP and broadly restrained mechanical stress-triggered actin polymerization. Mechanism studies revealed that GPER inhibited mechanical stress-mediated RhoA/LIMK/cofilin pathway, as well as the actin polymerization, by promoting expression of YAP and ARHGAP29, and the YAP nuclear localization, eventually causing the inhibition of Piezo1. YAP was obviously decreased in degenerated cartilage. Silencing YAP caused significantly increased actin polymerization and activation of Piezo1, and an increase of chondrocyte apoptosis. In addition, intra-articular injection of G-1 to OA rat effectively attenuated cartilage degeneration. CONCLUSION: We propose a novel regulatory mechanism underlying mechanical stress-mediated apoptosis of chondrocyte and elucidate the potential application value of GPER as therapy targets for OA.

Exploring the impact of pathogenic microbiome in orthopedic diseases: machine learning and deep learning approaches.

Osteoporosis, arthritis, and fractures are examples of orthopedic illnesses that not only significantly impair patients' quality of life but also complicate and raise the expense of therapy. It has been discovered in recent years that the pathophysiology of orthopedic disorders is significantly influenced by the microbiota. By employing machine learning and deep learning techniques to conduct a thorough analysis of the disease-causing microbiome, we can enhance our comprehension of the pathophysiology of many illnesses and expedite the creation of novel treatment approaches. Today's science is undergoing a revolution because to the introduction of machine learning and deep learning technologies, and the field of biomedical research is no exception. The genesis, course, and management of orthopedic disorders are significantly influenced by pathogenic microbes. Orthopedic infection diagnosis and treatment are made more difficult by the lengthy and imprecise nature of traditional microbial detection and characterization techniques. These cutting-edge analytical techniques are offering previously unheard-of insights into the intricate relationships between orthopedic health and pathogenic microbes, opening up previously unimaginable possibilities for illness diagnosis, treatment, and prevention. The goal of biomedical research has always been to improve diagnostic and treatment methods while also gaining a deeper knowledge of the processes behind the onset and development of disease. Although traditional biomedical research methodologies have demonstrated certain limits throughout time, they nevertheless rely heavily on experimental data and expertise. This is the area in which deep learning and machine learning approaches excel. The advancements in machine learning (ML) and deep learning (DL) methodologies have enabled us to examine vast quantities of data and unveil intricate connections between microorganisms and orthopedic disorders. The importance of ML and DL in detecting, categorizing, and forecasting harmful microorganisms in orthopedic infectious illnesses is reviewed in this work.

Microenvironmental interference with intra-articular stem cell regeneration influences the onset and progression of arthritis.

Studies have indicated that the preservation of joint health and the facilitation of damage recovery are predominantly contingent upon the joint's microenvironment, including cell-cell interactions, the extracellular matrix's composition, and the existence of local growth factors. Mesenchymal stem cells (MSCs), which possess the capacity to self-renew and specialize in many directions, respond to cues from the microenvironment, and aid in the regeneration of bone and cartilage, are crucial to this process. Changes in the microenvironment (such as an increase in inflammatory mediators or the breakdown of the extracellular matrix) in the pathological context of arthritis might interfere with stem cell activation and reduce their ability to regenerate. This paper investigates the potential role of joint microenvironmental variables in promoting or inhibiting the development of arthritis by influencing stem cells' ability to regenerate. The present status of research on stem cell activity in the joint microenvironment is also outlined, and potential directions for developing new treatments for arthritis that make use of these intervention techniques to boost stem cell regenerative potential through altering the intra-articular environment are also investigated. This review's objectives are to investigate these processes, offer fresh perspectives, and offer a solid scientific foundation for the creation of arthritic treatment plans in the future.

Mechanism of Abnormal Chondrocyte Proliferation Induced by Piezo1-siRNA Exposed to Mechanical Stretch.

OBJECTIVE: To investigate the effect of small interfering RNA targeting mechanosensitive ion channel protein Piezo1 (Piezo1-siRNA) on abnormal chondrocyte proliferation exposed to mechanical stretch. METHODS: Construct and screen effective Piezo1-siRNA sequences and explore an appropriate method to transfect lentiviral vector into chondrocytes exposed to mechanical stretch. Western blot and RT-PCR were used to detect the mRNA and protein expression of Piezo1, Kif18A, and ß-tubulin, respectively. Flow cytometry was used to measure the changes in the chondrocyte cycle. The proliferation of chondrocyte was evaluated by cell counting kit-8. RESULTS: According to the mRNA and protein expression of Piezo1, the effective siRNA sequence was successfully screened. Compared with the 0 h group, mechanical stretch upregulated the expression of Piezo1, Kif18A, and ß-tubulin, resulting in chondrocyte cycle arrest and eventually inhibiting chondrocyte proliferation. Moreover, Piezo1-siRNA transfection effectively blocks this process and promotes the proliferation of chondrocyte. CONCLUSION: Piezo1-siRNA can reduce the inhibition of chondrocyte proliferation induced by mechanical stretch via downregulating the expression of Kif18A and inhibiting the depolymerization of microtubules. Piezo1-siRNA plays a protective role in chondrocytes, which provides a potential method for the treatment of OA under abnormal mechanical stimulation.

Piezo1 activates the NLRP3 inflammasome in nucleus pulposus cell-mediated by Ca2+/NF-κB pathway.

Studying and understanding the mechanism of inflammation in nucleus pulposus is the key to understand and prevent intervertebral disc degeneration. We propose a model of mechanical sensitive ion channel Piezo1 mediated inflammation of nucleus pulposus cells. Piezo1 can up-regulate the level of interleukin-1ß (IL-1ß) in nucleus pulposus cells once it is activated. It is suggested that Piezo1 may mediate inflammation by activating Nod-like receptor protein 3 (NLRP3) inflammasome to accelerate the production and maturation of IL-1ß. The primary objective of this study was to explore whether Piezo1 activates NLRP3 inflammasome in nucleus pulposus cells. Piezo1 sensitization was induced by mechanical stretch following which we analyzed the priming and assembly of NLRP3 inflammasome and also studied if the downstream Ca2+/NF-κB pathway mediated this activation in nucleus pulposus cells. The expression of Piezo1 and NLRP3 inflammasome increased in a time-dependent manner upon mechanical stretch. Piezo1 activation promoted NLRP3 inflammasome assembly, which was demonstrated by the upregulation of caspase-1 activation and IL-1ß production. Transfection of Piezo1-siRNA reversed this process. The inhibition of Ca2+/NF-κB pathway reduced Piezo1-dependent activation of NLRP3 inflammasome. Thus, we propose that activation of NLRP3 inflammasome in nucleus pulposus cells mediated by Piezo1 through the Ca2+/NF-κB pathway is a novel pathogenesis for the progress of intervertebral disc degeneration. As per our knowledge this is the first study which has provided evidence linking Piezo1-mediated inflammation in nucleus pulposus cells with the production of NLRP3 inflammasome.