RESUMEN
Background: Although dual-plane subpectoral breast reconstruction has been widely implemented in implant-based breast reconstruction, animation deformities remain an issue. Recent advances in skin flap circulation detection have increased the use of prepectoral reconstruction. A partial muscle-splitting subpectoral plane was introduced to decrease the visibility of the implant edge. However, there is yet to be a direct comparison of these methods for optimal results, including changes in implant position after reconstruction. This study aims to compare the incidence of complications such as rippling, animation deformity, implant upward migration between the dual-plane, the partial muscle splitting subpectoral and the prepectoral reconstruction group. In addition, multivariate analysis was conducted to identify the risk factors of complications. Methods: We retrospectively investigated 349 patients who underwent unilateral direct-to-implant breast reconstruction from January 2017 to October 2020. Implants were inserted into the dual-plane subpectoral (P2) or partial muscle-splitting subpectoral (P1, the muscle slightly covering the upper edge of the implant) or the prepectoral pocket (P0). Postoperative outcomes and at least 2 years of follow-up complications were compared. Results: There was no significant difference in rippling (P=0.62) or visible implant edges on the upper pole (P=0.62) among the three groups. In contrast, the P0 group had a lower incidence of seroma (P=0.008), animation deformity (P<0.001), breast pain (P=0.002), and upward implant migration (P0: 1.09%, P1: 4.68%, P2: 38.37%, P<0.001). According to the multivariate analysis, P2 resulted in a greater risk of seroma (odds ratio: 4.223, P=0.002) and implant upward migration (odds ratio: 74.292, P<0.001) than did P0. Conclusions: P0 and P1 showed better postoperative outcomes than P2. Additionally, P0 had less implant migration than P1. Even though P1 minimally dissects the muscle, the location of the implant may change. Considering that muscle contraction can deteriorate symmetry and aesthetic results, the P0 method may be the most favorable.
RESUMEN
Osteomorphs are a newly described osteoclast lineage cell in mice, which are suggested to play a significant role in the maintenance of bone resorption. Preclinical investigations revealed that osteomorphs are generated through the fission of multinucleated bone-resorbing osteoclasts and can also re-fuse with existing osteoclasts. Modifications to RANKL signaling have been shown to alter cycles of fission and re-fusion of osteomorphs in mice. These novel findings were also shown to contribute to the rebound phenomenon after cessation of anti-RANKL therapy in mice. Moreover, the absence of osteomorph-specific genes in mice exhibits bone structural and quality phenotypes. Given these insights, it could be speculated that osteomorphs play a significant role in bone homeostasis, bone metabolic diseases, and response to therapeutics. In this review, we discuss these potential translational roles for osteomorphs. Importantly, we highlight the need for future preclinical and clinical studies to verify the presence of osteomorphs in humans and explore further the translational implications of this discovery.
RESUMEN
Osteoclasts are multinucleated bone-resorbing cells and a key player in bone remodeling for health and disease. Since the discovery of osteoclasts in 1873, the structure and function of osteoclasts and the molecular and cellular mechanisms of osteoclastogenesis have been extensively studied. Moreover, it has been well established that osteoclasts are differentiated in vitro from myeloid cells such as bone marrow macrophages or monocytes. The concept showing that osteoclasts are derived from a specific population (named osteoclast precursor cells [OCPs]) among myeloid cells has been long hypothesized. However, the specific precursor population of osteoclasts is not clearly defined yet. A growing body of work provides evidence of the developmental origin and lifespan of murine osteoclasts, particularly in vivo. Here, we review the emerging evidence that supports the existence of OCPs and discuss current insights into their identity.
RESUMEN
Scalp defects necessitate diverse approaches for successful reconstruction, taking into account factors such as defect size, surrounding tissue, and recipient vessel quality. This case report presents a challenging scenario involving a temporal scalp defect where ipsilateral recipient vessels were unavailable. The defect was effectively reconstructed utilizing a transposition flap and a latissimus dorsi free flap, which was anastomosed to the contralateral recipient vessels. Our report underscores the successful reconstruction of a scalp defect in the absence of ipsilateral recipient vessels, emphasizing the importance of employing appropriate surgical interventions without necessitating vessel grafts.
RESUMEN
BACKGROUND: Acellular dermal matrix (ADM) is generally used on implant-based breast operations; However, it can increase surgical site infection. Many immersion solutions are applied to ADM, however, the most effective solution is unknown. The purpose of this study is to determine the effect of different solutions on the biofilm formation and mechanical properties of ADM. METHODS: Aseptic porcine-derived ADMs were immersed in 5 different solutions for 30 min; sterile normal saline, 10% povidone-iodine, 0.5% chlorhexidine, antibiotics (cefazolin, gentamicin, and vancomycin), and taurolidine. They are transferred to 10 ml suspension of methicillin-sensitive/resistant Staphylococcus aureus (MSSA/MRSA) or Staphylococcus epidermidis and an overnight culture was performed. After rinsing and sonication to obtain the biofilm on ADM, colony forming unit (CFU) was measured. In addition, the maximum load before ADM deformation and the elongation length of ADM at the start of the maximum load was determined. RESULTS: Regardless of strains, povidone-iodine, chlorhexidine, and taurolidine group had lower CFUs than the saline group with statistical significance. Meanwhile, the antibiotics group did not show statistical difference from the saline group. Moreover, only taurolidine group showed higher tensile strength (MRSA, p = 0.0003; S. epidermidis, p = 0.0023) and elongation length (MSSA, p = 0.0015) than the saline group. The antibiotics and chlorhexidine group yielded lower tensile strength and elongation length than the povidone-iodine and taurolidine groups. CONCLUSIONS: It was suggested that the 10% povidone-iodine or taurolidine solution is effective. In contrast, the antibiotics solution could be considered as an effective intraoperative solution.
Asunto(s)
Dermis Acelular , Staphylococcus aureus Resistente a Meticilina , Animales , Porcinos , Povidona Yodada/farmacología , Clorhexidina/farmacología , Inmersión , Staphylococcus aureus , Antibacterianos/farmacología , BiopelículasRESUMEN
Bovine spastic paresis (BSP) is a neuromuscular disorder characterized by hypertension and stiffness of hindlimb. Two Korean native cattle (Hanwoo) calves developed BSP or BSP-like symptoms, and a tenotomy of superficial tendon of medial head and deep tendon of lateral head of gastrocnemius muscle was performed for treatment. A cast was applied postoperatively to prevent muscle rupture and was removed three weeks later. The prognosis was evaluated at 3 weeks, 6 and 18 months postoperatively. Neither calf showed any other postoperative sequelae. This is the first case study to report the diagnosis, treatment, and prognosis of BSP in Hanwoo.
Asunto(s)
Espasticidad Muscular , Tenotomía , Bovinos , Animales , Tenotomía/veterinaria , Espasticidad Muscular/cirugía , Espasticidad Muscular/veterinaria , Espasticidad Muscular/diagnóstico , Músculo Esquelético , Paresia/etiología , Paresia/cirugía , Paresia/veterinaria , República de CoreaRESUMEN
BACKGROUND: During breast reconstruction, predicting contralateral perfusion of the deep inferior epigastric artery perforator flap can help minimize tissue necrosis. This study aimed to quantify the area of contralateral perfusion and identify the factors affecting it. METHODS: A retrospective study was conducted on unilateral breast reconstructions with a single perforator-based deep inferior epigastric artery perforator flap, for the period of 2017 to 2019. Data on the distance between the perforator and the umbilicus, and the grade of the midline crossing-over vessel (G0, no vessel; G1, suspicious vessel; G2, definite vessel), were collected. Contralateral perfusion was estimated using intraoperative indocyanine green angiography, and the degree of contralateral circulation based on perforator location was assessed using a response surface methodology analysis. RESULTS: The study included 143 patients (G0, 62; G1, 45; and G2, 36). The average length of transverse contralateral flap perfusion (contralateral circulation area/vertical height of the flap) increased as the crossing-over vessel grade increased (G0, 62.96 ± 20.33 mm; G1, 71.69 ± 20.66 mm; and G2, 81.1 ± 19.32 mm; P = 0.0002). In the response surface methodology analysis, contralateral perfusion was the least when the perforator was located near the umbilicus (G0, within a 10-mm radius; G1, <10-mm transverse distance and 16- to 22-mm vertical distance; and G2, within a 20-mm radius). CONCLUSIONS: The umbilicus can interfere with contralateral perfusion; thus, a definite presence of a midline crossing-over vessel ensures robust contralateral perfusion. The results of this study can help surgeons select the optimal single perforator before surgery. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.
Asunto(s)
Mamoplastia , Colgajo Perforante , Humanos , Estudios Retrospectivos , Ombligo/cirugía , Mamoplastia/métodos , Colgajo Perforante/irrigación sanguínea , Perfusión , Arterias EpigástricasRESUMEN
Monocyte/macrophage lineage cells are highly plastic and can differentiate into various cells under different environmental stimuli. Bone-resorbing osteoclasts are derived from the monocyte/macrophage lineage in response to receptor activator of NF-κB ligand (RANKL). However, the epigenetic signature contributing to the fate commitment of monocyte/macrophage lineage differentiation into human osteoclasts is largely unknown. In this study, we identified RANKL-responsive human osteoclast-specific superenhancers (SEs) and SE-associated enhancer RNAs (SE-eRNAs) by integrating data obtained from ChIP-seq, ATAC-seq, nuclear RNA-seq and PRO-seq analyses. RANKL induced the formation of 200 SEs, which are large clusters of enhancers, while suppressing 148 SEs in macrophages. RANKL-responsive SEs were strongly correlated with genes in the osteoclastogenic program and were selectively increased in human osteoclasts but marginally presented in osteoblasts, CD4+ T cells, and CD34+ cells. In addition to the major transcription factors identified in osteoclasts, we found that BATF binding motifs were highly enriched in RANKL-responsive SEs. The depletion of BATF1/3 inhibited RANKL-induced osteoclast differentiation. Furthermore, we found increased chromatin accessibility in SE regions, where RNA polymerase II was significantly recruited to induce the extragenic transcription of SE-eRNAs, in human osteoclasts. Knocking down SE-eRNAs in the vicinity of the NFATc1 gene diminished the expression of NFATc1, a major regulator of osteoclasts, and osteoclast differentiation. Inhibiting BET proteins suppressed the formation of some RANKL-responsive SEs and NFATc1-associated SEs, and the expression of SE-eRNA:NFATc1. Moreover, SE-eRNA:NFATc1 was highly expressed in the synovial macrophages of rheumatoid arthritis patients exhibiting high-osteoclastogenic potential. Our genome-wide analysis revealed RANKL-inducible SEs and SE-eRNAs as osteoclast-specific signatures, which may contribute to the development of osteoclast-specific therapeutic interventions.
Asunto(s)
Células de la Médula Ósea , Osteoclastos , Ligando RANK , Humanos , Células de la Médula Ósea/metabolismo , Diferenciación Celular , Epigénesis Genética , Macrófagos/metabolismo , Factores de Transcripción NFATC/genética , Factores de Transcripción NFATC/metabolismo , Osteoclastos/metabolismo , Ligando RANK/genética , Ligando RANK/metabolismoRESUMEN
Treating osteoporosis and associated bone fractures remains challenging for drug development in part due to potential off-target side effects and the requirement for long-term treatment. Here, we identify recombinant adeno-associated virus (rAAV)-mediated gene therapy as a complementary approach to existing osteoporosis therapies, offering long-lasting targeting of multiple targets and/or previously undruggable intracellular non-enzymatic targets. Treatment with a bone-targeted rAAV carrying artificial microRNAs (miRNAs) silenced the expression of WNT antagonists, schnurri-3 (SHN3), and sclerostin (SOST), and enhanced WNT/ß-catenin signaling, osteoblast function, and bone formation. A single systemic administration of rAAVs effectively reversed bone loss in both postmenopausal and senile osteoporosis. Moreover, the healing of bone fracture and critical-sized bone defects was also markedly improved by systemic injection or transplantation of AAV-bound allograft bone to the osteotomy sites. Collectively, our data demonstrate the clinical potential of bone-specific gene silencers to treat skeletal disorders of low bone mass and impaired fracture repair.
Asunto(s)
Fracturas Óseas , Osteoporosis , Humanos , Proteínas Adaptadoras Transductoras de Señales/genética , Osteoporosis/genética , Osteoporosis/terapia , Fracturas Óseas/genética , Fracturas Óseas/terapia , Huesos , Terapia GenéticaRESUMEN
Loss to follow-up is inevitable in retrospective cohort studies, and patients are lost to follow-up after direct-to-implant reconstruction despite annual follow-up recommendation. We analyzed more than 500 patients to analyze the rate of loss to follow-up to plastic surgery and to investigate the factors affecting it. A retrospective review of patients who underwent direct-to-implant reconstruction between July 2008 and August 2016 was performed. Loss to follow-up to plastic surgery was defined as a difference of ≥24 months between the total and plastic surgery follow-up. The rate of loss to follow-up and associated factors including patients' demographics, surgery-related variables, oncological data, and early and late complications were analyzed. Of 631 patients who underwent direct-to-implant reconstruction, 551 patients continued visiting the hospital for breast cancer-related treatment. Of the 527 patients who were eligible for the study, 157 patients (29.8%) were lost to plastic surgery follow-up. Surgery-related variables, early complications, cancer stage, and adjuvant therapies were not significantly different. Younger age was significantly associated with loss to follow-up in univariate analysis. However, logistic regression revealed that a long total follow-up period, distant metastasis, and absence of late elective complications were significant factors contributing to follow-up loss. Late elective complications such as malposition, capsular contracture, and mastectomy flap thinning were more common in the follow-up group (48%) than in the loss to follow-up group (22%). Follow-up loss after direct-to-implant reconstruction was not associated with specific demographic or surgery-related variables, and postoperative courses significantly affected the loss to follow-up.
Asunto(s)
Implantación de Mama , Implantes de Mama , Neoplasias de la Mama , Mamoplastia , Humanos , Femenino , Mastectomía , Neoplasias de la Mama/cirugía , Estudios de Seguimiento , Estudios Retrospectivos , Implantes de Mama/efectos adversos , Resultado del Tratamiento , Mamoplastia/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/cirugía , Implantación de Mama/efectos adversosRESUMEN
Osteoclasts are the only cells that can efficiently resorb bone. They do so by sealing themselves on to bone and removing the mineral and organic components. Osteoclasts are essential for bone homeostasis and are involved in the development of diseases associated with decreased bone mass, like osteoporosis, or abnormal bone turnover, like Paget's disease of bone. In addition, compromise of their development or resorbing machinery is pathogenic in multiple types of osteopetrosis. However, osteoclasts also have functions other than bone resorption. Like cells of the innate immune system, they are derived from myeloid precursors and retain multiple immune cell properties. In addition, there is now strong evidence that osteoclasts regulate osteoblasts through a process known as coupling, which coordinates rates of bone resorption and bone formation during bone remodeling. In this article we review the non-resorbing functions of osteoclasts and highlight their importance in health and disease.
Asunto(s)
Resorción Ósea , Osteoclastos , Humanos , Osteoclastos/fisiología , Osteoblastos , Remodelación Ósea , HuesosRESUMEN
Hepatic alcohol clearance is a key factor to overcome alcohol hangovers, and over the period, alcohol hangovers may lead to inflammation and oxidative stress. Natural food products with high antioxidant and anti-inflammatory effects might contribute to hepatic alcohol clearance, a hypothesis in this study. The present study aimed to evaluate the influence of turmeric (Curcuma longa L., Zingiberaceae) is an herbal product having antioxidant and anti-inflammatory activities, on alcohol metabolism using binge alcohol drinking rat model. In vivo investigations revealed that pretreatment with turmeric extract enhanced alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activities upon binge ethanol (3 g/kg). Additionally, pretreatment with turmeric extract regulated CYP2E1 activity and levels of reactive oxygen species (ROS), Bax, Bcl-2, and inflammatory mediators like IL-1ß, IL-6, and TNF-α. Moreover, turmeric extract upregulated superoxide dismutase, catalase, and glutathione peroxidase activities in liver tissues. Together, these observations shed light on the potential beneficial effects of turmeric extract against acute liver toxicity. The results offer an alternative natural functional food product, turmeric extract, to prevent the negative implications of binge drinking.
RESUMEN
Osteoclasts are bone-resorbing cells that undergo extensive changes in morphology throughout their differentiation. Altered osteoclast differentiation and activity lead to changes in pathological bone resorption. The mammalian target of rapamycin (mTOR) is a kinase, and aberrant mTOR complex 1 (mTORC1) signaling is associated with altered bone homeostasis. The activation of mTORC1 is biphasically regulated during osteoclastogenesis; however, the mechanism behind mTORC1-mediated regulation of osteoclastogenesis and bone resorption is incompletely understood. Here, we found that MYC coordinates the dynamic regulation of mTORC1 activation during osteoclastogenesis. MYC-deficiency blocked the early activation of mTORC1 and also reversed the decreased activity of mTORC1 at the late stage of osteoclastogenesis. The suppression of mTORC1 activity by rapamycin in mature osteoclasts enhances bone resorption activity despite the indispensable role of high mTORC1 activation in osteoclast formation in both mouse and human cells. Mechanistically, MYC induces Growth arrest and DNA damage-inducible protein (GADD34) expression and suppresses mTORC1 activity at the late phase of osteoclastogenesis. Taken together, our findings identify a MYC-GADD34 axis as an upstream regulator of dynamic mTORC1 activation in osteoclastogenesis and highlight the interplay between MYC and mTORC1 pathways in determining osteoclast activity.
RESUMEN
BACKGROUND: Despite remarkable improvements in free flap procedures, partial flap losses in perforator flaps still occur. This study aimed to analyze partial necrosis cases that underwent reconstruction of the lower extremities using anterolateral thigh free flaps and to identify risk factors causing the occurrence of partial necrosis. METHODS: From January of 2005 to February of 2017, 303 anterolateral thigh free flaps were analyzed retrospectively. After collecting patient data, receiver operating characteristic curve analysis was conducted to find the critical distance between the perforator and the flap margin that distinguishes partial necrosis. Also, the rate of partial losses was calculated for each section after dividing the distance from the perforator to the flap margin into 1-cm sections. Lastly, logistic regression analyses were performed to identify the risk factors. RESULTS: Forty-three cases had partial flap loss (14.19 percent). Flaps with supradeep fat layer elevation showed the highest rate of partial necrosis (25.53 percent), with statistical significance ( p = 0.0001). In receiver operating characteristic curve analysis, the cutoff distance was 10.25 cm. In addition, flap tissues 8 cm away from the perforator have a 10.3 percent chance of necrosis, whereas those 12 cm away from the perforator have a 22.9 percent chance. Lastly, supradeep fat layer elevation (OR, 3.952) and large flap size (OR, 1.041) were risk factors for partial flap necrosis on multivariate analysis. CONCLUSIONS: The distance from the perforator to the flap margin, the flap elevation layer, and the flap size affected the occurrence of partial necrosis. Taking these into consideration, anterolateral thigh free flaps of appropriate size and thickness should be harvested. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.
Asunto(s)
Colgajos Tisulares Libres , Colgajo Perforante , Procedimientos de Cirugía Plástica , Traumatismos de los Tejidos Blandos , Humanos , Colgajos Tisulares Libres/cirugía , Estudios Retrospectivos , Procedimientos de Cirugía Plástica/efectos adversos , Procedimientos de Cirugía Plástica/métodos , Traumatismos de los Tejidos Blandos/etiología , Traumatismos de los Tejidos Blandos/cirugía , Extremidad Inferior/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Factores de Riesgo , Necrosis/cirugía , Colgajo Perforante/cirugíaRESUMEN
Osteoclasts are bone resorbing cells that are responsible for physiological and pathological bone resorption. Macrophage colony stimulating factor (M-CSF) binds to the M-CSF receptor (c-FMS) and plays a key role in the differentiation and survival of macrophages and osteoclasts. THOC5, a member of the THO complex, has been shown to regulate hematopoiesis and M-CSF-induced macrophage differentiation. However, the role of THOC5 in osteoclasts remains unclear. Here, our study reveals a new role of THOC5 in osteoclast formation. We found that THOC5 shuttles between nucleus and cytoplasm in an M-CSF signaling dependent manner. THOC5 bound to FICD, a proteolytic cleavage product of c-FMS, and THOC5 facilitates the nuclear translocations of FICD. Decreased expression of THOC5 by siRNA-mediated knock down suppressed osteoclast differentiation, in part, by regulating RANK, a key receptor of osteoclasts. Mechanistically, knock down of THOC5 inhibited the expression of RANKL-induced FOS and NFATc1. Our findings highlight THOC5's function as a positive regulator of osteoclasts.
Asunto(s)
Factor Estimulante de Colonias de Macrófagos , Proteínas Nucleares , Osteoclastos , Osteogénesis , Resorción Ósea , Diferenciación Celular , Humanos , Factor Estimulante de Colonias de Macrófagos/metabolismo , Factor Estimulante de Colonias de Macrófagos/farmacología , Proteínas Nucleares/metabolismo , Osteoclastos/metabolismoRESUMEN
Introduction: Breast reconstruction has become common after total mastectomy; however, certain types of breast reconstruction may be associated with delayed local recurrence or poor survival. Here, we investigated whether there are differences in the diagnosis and prognosis of local recurrence between autologous reconstruction and implant reconstruction. Materials and Methods: A retrospective analysis was performed on patients undergoing breast cancer surgery with autologous tissue or immediate implant reconstruction in a single center (January 2003-December 2017). Patient data including the period from cancer surgery to local recurrence diagnosis, tumor size at the time of recurrence, and survival time after cancer surgery and recurrence detection were analyzed. Results: There was a significant difference (p = 0.021) in the time from surgery to recurrence between the autologous tissue (1,246 days) and implant (909 days) groups. Recurrence tumor size did not differ (autologous: 1.00 cm2 vs. implant: 0.90 cm2; p = 0.813). Survival time after surgery (p = 0.63) and recurrence detection (p = 0.74) did not statistically significant. Conclusions: Statistical difference in the detection time was observed between autologous tissue and implant group. On the other hand, there is no difference in recurrence tumor size or survival time. A further study is necessary to identify the different detection time of local recurrence.
Asunto(s)
Implantes de Mama , Neoplasias de la Mama , Mamoplastia , Implantes de Mama/efectos adversos , Neoplasias de la Mama/patología , Femenino , Humanos , Mastectomía , Recurrencia Local de Neoplasia/cirugía , Pronóstico , Estudios RetrospectivosRESUMEN
Various synthetic and decellularized materials are being used to reconstruct peripheral nerve defects and replace autologous nerve grafts. In this study, we developed a microgel printing bath to three-dimensionally (3D) print a peripheral nervous system decellularized extracellular matrix nerve graft reinforced by a polycaprolactone (PCL) conduit. The straightforward fabrication method of an alginate microgel-supplemented printing bath allows a 30 µm filament resolution of a low viscous decellularized extracellular matrix hydrogel with neutral pH. When applied to a sciatic nerve defect model of rats, the total number of regenerated axons and relative gastrocnemius muscle weight ratio were comparable to those of the autologous nerve graft group. Meanwhile, the results were superior to those of the porcine decellularized nerve graft group or the 3D printed decellularized extracellular matrix graft group. This study will be the first step demonstrating that the 3D printed decellularized extracellular matrix (dECM) graft with a PCL conduit is an effective and reliable choice to replace an autologous nerve graft in the near future.
Asunto(s)
Microgeles , Citoesqueleto de Actina , Animales , Matriz Extracelular Descelularizada , Poliésteres , Impresión Tridimensional , Ratas , Nervio Ciático/cirugía , Porcinos , Ingeniería de Tejidos/métodos , Andamios del TejidoRESUMEN
OBJECTIVE: Hypoxia occurs in tumors, infections, and sites of inflammation, such as in the affected joints of patients with rheumatoid arthritis (RA). It alleviates inflammatory responses and increases bone resorption in inflammatory arthritis by enhancing osteoclastogenesis. The mechanism by which the hypoxia response is linked to osteoclastogenesis and inflammatory bone resorption is unclear. This study was undertaken to evaluate whether the protein lysine-specific demethylase 1 (LSD1) metabolically integrates inflammatory osteoclastogenesis and bone resorption in a state of inflammatory arthritis. METHODS: LSD1-specific inhibitors and gene silencing with small interfering RNAs were used to inhibit the expression of LSD1 in human osteoclast precursor cells derived from CD14-positive monocytes, with subsequent assessment by RNA-sequencing analysis. In experimental mouse models of arthritis, inflammatory osteolysis, or osteoporosis, features of accelerated bone loss and inflammatory osteolysis were analyzed. Furthermore, in blood samples from patients with RA, cis-acting expression quantitative trait loci (cis-eQTL) were analyzed for association with the expression of hypoxia-inducible factor 1α (HIF-1α), and associations between HIF-1α allelic variants and extent of bone erosion were evaluated. RESULTS: In human osteoclast precursor cells, RANKL induced the expression of LSD1 in a mechanistic target of rapamycin-dependent manner. Expression of LSD1 was higher in synovium from RA patients than in synovium from osteoarthritis patients. Inhibition of LSD1 in human osteoclast precursors suppressed osteoclast differentiation. Results of transcriptome analysis identified several LSD1-mediated hypoxia and cell-cycle pathways as key genetic pathways involved in human osteoclastogenesis. Furthermore, HIF-1α protein, which is rapidly degraded by the proteasome in a normoxic environment, was found to be expressed in RANKL-stimulated osteoclast precursor cells. Induction of LSD1 by RANKL stabilized the expression of HIF-1α protein, thereby promoting glycolysis, in conjunction with up-regulation of the transcription factor E2F1. Analyses of cis-eQTL revealed that higher HIF-1α expression was associated with increased bone erosion in patients with RA. Inhibition of LSD1 decreased pathologic bone resorption in mice, both in models of accelerated osteoporosis and models of arthritis and inflammatory osteolysis. CONCLUSION: LSD1 metabolically regulates osteoclastogenesis in an energy-demanding inflammatory environment. These findings provide potential new therapeutic strategies targeting osteoclasts in the management of inflammatory arthritis, including in patients with RA.
Asunto(s)
Artritis Reumatoide , Resorción Ósea , Factor de Transcripción E2F1 , Subunidad alfa del Factor 1 Inducible por Hipoxia , Osteólisis , Osteoporosis , Animales , Resorción Ósea/metabolismo , Resorción Ósea/patología , Diferenciación Celular , Hipoxia de la Célula , Factor de Transcripción E2F1/metabolismo , Histona Demetilasas/genética , Histona Demetilasas/metabolismo , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Ratones , Osteoclastos/metabolismo , Osteoclastos/patología , Osteólisis/metabolismo , Osteólisis/patología , Osteoporosis/metabolismo , Osteoporosis/patología , Ligando RANK/metabolismoRESUMEN
BACKGROUND AND OBJECTIVES: Despite advances in medicine, infection at the surgical site is an impregnation problem that most surgeons confront. Although studies on the seasonality of infection have been conducted in various areas, no study has confirmed the relationship between seasonal temperature and infection after breast reconstruction. METHODS: From 2008 to 2018, a retrospective study was conducted on patients who underwent implant-based breast reconstruction. Patient demographics, intraoperative data, postoperative data, and temperature information were collected. Temperature differences between cases with and without infection were examined. The differences in the incidence and risk of infection by season were estimated according to the hot season (July to August) and the nonhot season (September to June). RESULTS: Of the 460 cases enrolled, 42 cases developed an infection. Among them, 15 (35.71%) cases developed infection during the hot season (P = 0.003). According to the logistic regression model, the risk of infection was 2.639 times higher in the hot season than in the nonhot season (95% confidence interval, 1.282-5.434; P = 0.008). When the temperature was higher than 25°C, the risk of infection increased by 45.2% for every 1°C increase, which was statistically significant (odds ratio, 1.452; 95% confidence interval, 1.198-1.76; P < 0.001). CONCLUSION: In conclusion, the hot season or average temperatures higher than 25°C increase the risk of infection in patients undergoing implant-based breast reconstruction. It is essential to focus on skin hygiene during the healing of the incision site.