Residue quality drives SOC sequestration by altering microbial taxonomic composition and ecophysiological function in desert ecosystem.

Plant residues are important sources of soil organic carbon in terrestrial ecosystems. The degradation of plant residue by microbes can influence the soil carbon cycle and sequestration. However, little is known about the microbial composition and function, as well as the accumulation of soil organic carbon (SOC) in response to the inputs of different quality plant residues in the desert environment. The present study evaluated the effects of plant residue addition from Pinus sylvestris var. mongolica (Pi), Artemisia desertorum (Ar) and Amorpha fruticosa (Am) on desert soil microbial community composition and function in a field experiment in the Mu Us Desert. The results showed that the addition of the three plant residues with different C/N ratios induced significant variation in soil microbial communities. The Am treatment (low C/N ratio) improved microbial diversity compared with the Ar and Pi treatments (medium and high C/N ratios). The variations in the taxonomic and functional compositions of the dominant phyla Actinobacteria and Proteobacteria were higher than those of the other phyla among the different treatments. Moreover, the network links between Proteobacteria and other phyla and the CAZyme genes abundances from Proteobacteria increased with increasing residue C/N, whereas those decreased for Actinobacteria. The SOC content of the Am, Ar and Pi treatments increased by 45.73%, 66.54% and 107.99%, respectively, as compared to the original soil. The net SOC accumulation was positively correlated with Proteobacteria abundance and negatively correlated with Actinobacteria abundance. These findings showed that changing the initial quality of plant residue from low C/N to high C/N can result in shifts in taxonomic and functional composition from Actinobacteria to Proteobacteria, which favors SOC accumulation. This study elucidates the ecophysiological roles of Actinobacteria and Proteobacteria in the desert carbon cycle, expands our understanding of the potential microbial-mediated mechanisms by which plant residue inputs affect SOC sequestration in desert soils, and provides valuable guidance for species selection in desert vegetation reconstruction.

Serious Condylar Head Absorption in Children With Intracapsular Condylar Fractures Treated Operatively With Long Screws.

OBJECTIVE: This study was performed to explore bone remodelling in children with intracapsular condylar fractures after the condylar fracture fragments were fixed using long screws and to offer possible explanations about the underlying mechanism. PATIENT AND METHODS: Records of children (less than 12 y old) who sustained intracapsular condylar fractures and fixed with long screws from May 2012 to January 2015 were retrieved. Age, gender, dates of injury, admission, and discharge, mechanism of trauma, location and pattern of fracture, other mandibular fractures, treatment methods, and time of review were recorded and analyzed. Image dates of pretreatments and posttreatments, including the date of review, were also recorded. RESULTS: A total of 8 patients completed their follow-up, and all patients (n=5) who were followed up after more than 3 months showed serious resorption of the condylar head. The condylar head resorbed until the height (or articular surface) dropped and aligned with the surface of the screw. The shortest time of absorption, as shown by the computed tomography scan was 106 days, and the longest time was 171 days (average time of 141.8 d). CONCLUSIONS: Intracapsular condyle fractures in children should be managed conservatively as much as possible. However, if the height of the fracture fragments drops remarkably, open reduction and rigid internal fixation become possible choices.

Exogenous adenosine activates A2A adenosine receptor to inhibit RANKL-induced osteoclastogenesis via AP-1 pathway to facilitate bone repair.

BACKGROUND: Adenosine is a purine nucleoside involved in regulating bone homeostasis through binding to A1, A2A, A2B, and A3 adenosine receptors (A1R, A2AR, A2BR, and A3R, respectively). However, the underlying mechanisms by which adenosine and receptor subtypes regulate osteoclast differentiation remain uncertain. This study aims to assess the role of exogenous adenosine and receptor subtypes in receptor activator of NF-κB ligand (RANKL)-induced osteoclast formation and explore the underlying molecular mechanisms. METHODS AND RESULTS: The nanofibrous mats incorporated with adenosine exhibited robust ability to facilitate rat critical-size calvarial defect healing with decreased number of osteoclasts. Moreover, exogenous adenosine substantially enhanced the expression of A2AR and suppressed tartrate-resistant acid phosphatase-positive osteoclast formation and expression of osteoclast-related genes Ctsk, NFATc1, MMP9, and ACP5. This enhancement and suppression could be reversed by adding an A2AR antagonist, ZM241385, in RAW264.7 cells. Finally, RNA sequencing showed that the expression of Fos-related antigen 2 (Fra2) was distinctly downregulated through stimulation of adenosine in RAW264.7 cells treated with RANKL. This downregulation was reversed by ZM241385 according to real-time PCR, Western blot, and immunofluorescence analyses. CONCLUSIONS: These findings demonstrated that exogenous adenosine binding to A2AR attenuated osteoclast differentiation via the inhibition of activating protein-1 (AP-1, including Fra2 subunit) pathway both in vitro and in vivo.

Treatment of Sagittal Fracture of the Mandibular Condyle Using Resorbable-Screw Osteosynthesis.

PURPOSE: Screw osteosynthesis is advocated for the treatment of sagittal fracture of mandibular condyle (SFMC). This study aimed to explore the applicability of resorbable-screw osteosynthesis in the treatment of SFMC. METHODS: A retrospective cohort study was performed in patients with SFMC treated with resorbable-screw osteosynthesis (group A) from June 2011 through June 2021. The patients who had undergone titanium-screw osteosynthesis served as the control group (group B). The primary outcome variable was fracture healing, defined as follows: 1) normal mouth opening and restoration of pretrauma occlusion; 2) without complications or discomfort of temporomandibular joint symptoms; and 3) fracture union without abnormal reactions or bone resorption in computed tomography images. The secondary outcome variable was condylar morphological changes including radiographic imaging appearance of the condyle, mandibular ramus height (MRH), anteroposterior diameter (APD), and mediolateral diameter (MLD) of the condyle, which were assessed by comparing the computed tomography images 1 week after surgery with those of 3 months after surgery. The collected data of the outcome variables of the 2 groups were analyzed correspondingly using Student's paired t test and Student's t test. RESULTS: There were 24 patients in group A and 71 patients in group B. All the patients displayed an evident improvement in mouth opening and restored pretrauma occlusion. Few patients had complications (group A, 8.33%; group B, 9.86%) and discomfort of temporomandibular joint symptoms (group A, 16.67%; group B, 15.49%). Fracture union without abnormal reactions or bone resorption was observed during the follow-up. The radiographic evaluation revealed no significant difference in the MRH, the maximum APD, and MLD of the condyles between 1 week and 3 months after surgery in both groups. There were no significant intergroup differences in the changes in the MRH, APD, and MLD of the condyles. CONCLUSIONS: Resorbable-screw osteosynthesis is a viable option for the treatment of SFMC.

Design and Use of a Pair of Computer-Designed Surgical Templates in Reduction of a Comminuted Zygomatic Arch Fracture.

BACKGROUND: Isolated depressed zygomatic arch fractures are often treated with closed reduction. Reduction is usually performed through the Gillies approach or Keen approach. comminuted zygomatic arch fractures generally require open reduction and fixation to achieve good results. This article describes how to use a pair of surgical templates to assist in the fixation of comminuted zygomatic arch fractures with absorbable plates. METHODS: A pair of computer-designed surgical templates were applied to restore the main part of zygomatic arch. Placing a surgical template on the medial side of the zygomatic arch can provide a supporting force and improves the stability of the reduced bone fragments. The lateral template of zygomatic arch limits the excessive uplift of bone fragments. RESULTS AND DISCUSSION: The operation was performed according to the predetermined procedure. Postoperative computed tomography showed satisfactory reduction effect. In conclusion, with the aid of surgical templates, the reduction and fixation of comminuted zygomatic arch fractures can be more easily performed using absorbable plates.

Removal of Fracture Fragments in Intracapsular Condylar Fractures: An Alternative Treatment Option.

OBJECTIVE: This study aimed to explore bone remodeling after condylar fracture fragments have been removed from patients with intracapsular condylar fractures. it also evaluated whether condyle fracture removal can be used alternatively when the authors treat patients with comminuted or small pieces of fracture or in extremely difficult operations. METHODS: Records of patients who sustained intracapsular condylar fractures and treated by removal of fragments for the period of February 2013 to September 2019 were retrieved. Data about age, gender, date of injury, dates of admission and discharge, mechanism of trauma, location and pattern of fracture, other mandibular fracture, treatment methods and time of review were recorded and analyzed. Image dates of pre- and post-treatment (including the time of review) were also recorded. RESULTS: The data of a total of 103 patients ranging from 5 to 84 years old were retrieved during this study. A total of 135 sides of condylar fragments were removed. Almost all of the patients with comminuted condyle head fracture or type A fracture presented apparent shortening of the ramus height, and none of them showed osteogenesis (or new bone formation) during their follow-up. Present study only observed osteogenesis in few patients who sustained type B/C intracapsular condylar fractures during their follow-up. The younger the patient was, the longer the follow-up time was, and the higher the possibility of new bone formation was. No correlation was found between the amount of osteogenesis and follow-up time, the amount of osteogenesis was generally small, and no patient could form a new condyle head similar to the normal (or original) condyle head. Condylar hypertrophy only occurred in children. Four patients developed temporomandibular joint ankylosis. CONCLUSIONS: Removal of fracture fragments is an alternative treatment option for patients who sustained comminuted or small pieces of fracture or in extremely difficult operations.

Digital Design and Application of 3D Printed Surgical Guide for Long Screw Fixation of Condylar Sagittal Fracture.

OBJECTIVE: To explore a digital solution for long screw fixation of condylar sagittal fracture, and to achieve accurate positioning of the long screw. METHODS: The CT data of the patient with condylar sagittal fracture was imported into Materialise Mimics, and the fractures were reduced by virtual surgery. The surgical guide for long screw fixation was designed in Materialise 3-matic, and then 3D printed for intraoperative assistance. RESULTS: With the help of the 3D printed surgical guide, the long screw used to fix condylar sagittal fracture was accurately positioned, which was completely consistent with the preoperative design. CONCLUSION: The digitally designed 3D printed surgical guide is an effective way to achieve accurate positioning of the long screw fixation of condylar sagittal fracture.

Maxillofacial Injuries in Pediatric Patients.

OBJECTIVE: This study aimed to evaluate and analyse the demographic characteristics and changes in maxillofacial injuries during their development in pediatric patients. METHODS: A retrospective cohort and case-control study was conducted. The sample was composed of all children (less than 10.5 years) who presented with maxillofacial injuries within a 6.5-year period (from December 2012 to April 2019). Data about age, gender, hospitalization date, mechanism of trauma, location and pattern of injuries, associated general injuries or systemic diseases, admission methods (emergency admission or not), type of anesthesia, treatment methods and hospital costs (¥) were recorded and analyzed. Data analysis included Chi-square test, Fisher exact test, and t test. Univariate and multivariate analyses were also performed. Logistic regression analysis was used to control for confounding variables. Differences at P < 0.05 were considered significant. RESULTS: A total of 643 pediatric patients were included in this study, with a boy-to-girl ratio of 1.77:1 (411 boys and 232 girls). The age range was 0.18 to 10.5 years (average of 3.23 ±â€Š1.98 years). The largest age group was patients aged 1 to 2 years (200 patients, 31.1%), followed by 2 to 3 years (139 patients, 21.6%). In the majority of patients, fall at ground level was the most common mechanism of injury (391 patients, 60.8%). In addition, 613 patients (95.3%) sustained at least maxillofacial soft-tissue injuries, while 460 (71.5%) sustained only maxillofacial soft-tissue injuries and 183 (28.5%) sustained maxillofacial fractures. Lip was the most vulnerable soft tissue to be injured (283 patients, 44.0%). Patients who sustained maxillofacial soft-tissue injuries were less prone to maxillofacial fractures than those who did not. Maxillofacial fractures were highly presented in patients with dental injuries (OR = 6.783; 95% confidence interval, 3.147-14.620; P < 0.001). Older children (> 5 years old) were at higher risk of maxillofacial fractures than younger children (≤ 5 years old, P = 0.006). The risk of maxillofacial fractures (except symphysis fractures) increased with age, especially in patients aged between 5 and 10 years. Maxillofacial soft-tissue injuries were highly distributed amongst patients aged 1 to 5 years. The number of patients who sustained only maxillofacial soft-tissue injuries gradually decreased from 2013 to 2018. Patients in emergency admission (OR = 13.375; 95% confidence interval, 1.286-139.121; P = 0.030) and treated under general anesthesia (OR = 27015.375; 95% confidence interval, 1033.046-706484.218; P < 0.001) were more prone to be treated by surgery procedure. Patients with facial fractures were less frequent to be treated by surgery procedure (OR = 0.006; 95% confidence interval, 0.000-0.575; P = 0.028); however, the mandibular symphysis (OR = 18.141; 95% confidence interval, 2.860-115.069; P = 0.002) or body fractures (OR = 71.583; 95% confidence interval, 2.358-2172.879; P = 0.014) were highly treated by surgery procedure. CONCLUSIONS: Maxillofacial fractures in pediatric patients were significantly related to age, etiology, maxillofacial soft-tissue injury, dental injury and other general injuries. Older pediatric patients were at higher risk of maxillofacial fractures (except symphysis fractures) and lower risk of maxillofacial soft-tissue injuries than younger pediatric patients. Patients in emergency admission, fractures of the symphysis or body, and treated under general anesthesia were the main reasons for surgical management.

Restoration of Ramus Height in Child Patients With Extracapsular Condylar Fractures: Is This Mission Almost Impossible to Accomplish?

OBJECTIVE: This study aimed to assess whether ramus height is restored in children with extracapsular condylar fractures treated by conservative or surgery procedures. METHODS: The sample consisted of 35 children (collected consecutively) less than 12 years old who presented with extracapsular condylar fractures and treated within an 8-year period (June 2011 to April 2019). Data on the age, gender, date of injury, mechanism of trauma, location and pattern of mandibular condylar fracture, associated injuries and treatment methods were recorded and analyzed. Ramus height restoration is the main evaluation indicator during the follow-up period. RESULTS: Within the 8-year record retrieval, the 35 children sustained 41 extracapsular condylar fractures. For the sample size, 10 (24.4%) and 31 (75.6%) had condylar neck and base fractures, respectively. Deviation and green-stick fracture were the predominant types in condylar neck and base fractures, accounting for more than 3 quarters (31, 75.6%). The majority (33, 80.5%) of patients were treated with nonsurgical treatment, and 8 (19.5%) were treated by open reduction and internal fixation (ORIF). During the follow-up period (1-1419 days, average time of 110.6 days), only 1 patient (with bilateral extracapsular condylar fractures) had their ramus height restored (follow-up period, 256 days). Most members of the ORIF group (5 of 8, 62.5%) postoperatively showed bended ramus (deviated angularly/fragment angulation). CONCLUSION: Conservative treatment could hardly restore the ramus height of children with extracapsular condylar fractures. Anatomically or totally restoring the ramus height is difficult even with the surgical treatment of ORIF; however, surgical treatment of ORIF can substantially restore the ramus height for dislocated fractures or seriously displaced fractures.

Extracapsular Condylar Fractures Treated Conservatively in Children: Mechanism of Bone Remodelling.

OBJECTIVE: This study aims to reveal the reconstruction process in pediatric patients with extracapsular condylar fractures after conservative treatment. We clarify that the "upright" position (or "recontouring" or favorable prognosis) of condyles is not a result of the anatomical reduction of the deviated condylar processes but originates from the remodeling of the skeleton. We also explore the related mechanism. METHODS: The sample consisted of 27 pediatric patients aged less than 12 years who presented with extracapsular condylar fractures and were treated conservatively within an 8-year period (June 2011-April 2019). Data on the age, gender, date of injury, mechanism of trauma, location and pattern of mandibular condylar fracture and associated injuries and treatment methods of the patients were obtained. The process of bone remodeling in condyles was also recorded and analyzed. RESULTS: The 27 children in this study sustained 33 extracapsular condylar fractures over the 8-year period of record retrieval. Amongst these fractures, 8 (24.2%) and 25 (75.8%) were condylar neck and condylar base fractures, respectively. Deviation and green-stick fractures were the predominant types and accounted for over 3 quarters of the condylar neck and base fractures (28, 84.8%), followed by dislocation fracture (3, 9.1%), displacement fracture (1, 3.0%), and non-displaced fracture (1, 3.0%). The period of follow-up ranged from 2 days to 257 days (average, 58.78 days). Only 1 patient with bilateral extracapsular condylar fractures showed vertically reconstructed condyles, which indicates an upright position of the condylar processes. One patient showed less angulation after treatment than before treatment, 1 patient revealed greater angulation after treatment than before treatment and all other patients (20 patients) showed the same angulation pre- and post-treatment. Both patients with only extracapsular condylar fractures showed no obvious deviations in dentition and facial asymmetry after their injury and treatment. The shortest and longest times observed for bone remodeling were 33 and 256 days, respectively. Children whose condylar head remained completely or at least partly inside the glenoid fossa showed satisfactory remodeling results during follow-up. Computed tomography scan during follow-up generally showed bone regeneration in the lateral condyle articular surface and the medial portion of the ascending ramus and bone resorption in the displaced direction (ie, the medial condyle head became sharp). Condylar heads displaced completely outside of the glenoid fossa showed serious shortening of the ascending ramus, and no obvious bone remodeling was observed. Only 1 patient with bilateral extracapsular condylar fractures showed a normal contour (ie, a vertically reconstructed condyle reflecting the upright position of the condylar processes) after 8 months. CONCLUSION: Stress stimulation originating from the glenoid fossa and ascending ramus of the mandible is a prerequisite for good condylar reconstruction. Conservative treatment could be carried out if the condylar head remains completely or at least partly inside the glenoid fossa. When the condylar head is dislocated completely outside the glenoid fossa, the glenoid-condylar relationship ceases to exist, joint function is lost and the height of the ascending ramus is significantly reduced. In this case, open reduction may be suitable.

Characteristic changes of traumatic dental injuries in a teaching hospital of Wuhan under transmission control measures during the COVID-19 epidemic.

BACKGROUND/AIMS: In December 2019, a novel coronavirus emerged in Wuhan City, and a retrospective analysis is necessary to provide clinicians with the characteristics of traumatic dental injuries (TDIs) during the epidemic. The aim of this study was to evaluate the changes in the characteristics of TDIs under the transmission control measures in Wuhan City utilizing an epidemiologic investigation. MATERIALS AND METHOD: In this retrospective study, epidemiologic information, including the number of patients, gender, age, and TDI parameters such as time since injury to the clinic visit, etiology, tooth location, and the type of injury was extracted from the records of patients in the hospital from two periods: period 1 (between January 23, 2020, and April 7, 2020) and period 2 (between January 23, 2019, and April 7, 2019). The data from the two periods were compared and analyzed. RESULT: A total of 158 patients were treated for TDIs (120 in 2019 and 38 in 2020). Males were more likely to suffer from TDIs than females with a ratio of 1.5:1, both in 2020 and 2019. Other than that, there were characteristic changes in TDIs during the transmission control measures in the COVID-19 epidemic, which included the number of patients, age, time since injury to the clinic visit, etiology, tooth location and the type of TDI. CONCLUSION: The transmission control measures during the COVID-19 epidemic had a significant impact on the epidemiology and etiology of TDIs in Wuhan City.

Connective tissue growth factor (CCN2) inhibits TNF-α-induced apoptosis by enhancing autophagy through the Akt and Erk pathways in osteoblasts.

Connective tissue growth factor (CTGF/CCN2) is a secreted protein modulating various biological processes, such as proliferation, differentiation, and survival. Tumor necrosis factor-α (TNF-α), known as a proinflammatory factor, negatively regulates osteoblast differentiation and survival. However, the potential mechanisms of CCN2 in TNF-α-induced osteoblast apoptosis are not fully understood. In the present study, we found that CCN2 was expressed in osteoblasts and downregulated after treatment with TNF-α. Overexpression of CCN2 attenuated TNF-α-induced osteoblast apoptosis. Autophagy, a pro-survival biological behavior, was triggered by TNF-α stimulation, and CCN2 overexpression enhanced this process. Inhibition of autophagy by chloroquine (CQ) affected the anti-apoptotic effect of CCN2. Moreover, the phosphorylation levels of Akt and Erk were upregulated in CCN2-over expressed cells, and LY294002 and U1026 (which inhibited the Akt and Erk signaling pathways, respectively) reversed the effect of CCN2 on autophagy and cell survival enhancement. Our data suggest that CCN2 might be a positive regulator of osteoblast survival in TNF-α stimulation by enhancing autophagy through the Akt and Erk signaling pathways.

Inhibition of JAK2 by AG490 promotes TNF-α-induced apoptosis by inhibiting autophagy in MC3T3-E1 cells.

Tumor necrosis factor-alpha (TNF-α), one of the pro-inflammatory factors in osteoporosis, has a strong enhancement effect on osteoclastogenesis and disruption of osteoblast survival and function. JAK2 participates in a wide range of biological processes, including bone homeostasis, but its function in osteoblast survival in inflammatory environments remains unknown. In this study, flow cytometry and immunofluorescence staining of LC3B were performed under TNF-α stimulation in MC3T3-E1 cells. Apoptosis-related protein Cleaved PARP and autophagy-related protein LC3 were upregulated, meanwhile, p62 was downregulated by TNF-α. JAK2 signaling was also activated in the process. AG490 was used to inhibit JAK2 signaling, which promoted apoptosis and attenuated autophagy induced by TNF-α. Enhancement of autophagy by rapamycin reversed the promotional effect of AG490 on apoptosis, and the autophagy inhibitor chloroquine further enhanced apoptosis. Western blot analysis showed that the STAT3, Akt, and Erk signaling pathways are involved in AG490 treatment. This study demonstrated for the first time that JAK2 inhibition by AG490 may play a crucial role in TNF-α-induced apoptosis by inhibiting autophagy and inhibiting the STAT3, Akt, and Erk signaling pathways.

Cellular hypoxia promotes osteogenic differentiation of mesenchymal stem cells and bone defect healing via STAT3 signaling.

BACKGROUND: Hypoxia in the vicinity of bone defects triggers the osteogenic differentiation of precursor cells and promotes healing. The activation of STAT3 signaling in mesenchymal stem cells (MSCs) has similarly been reported to mediate bone regeneration. However, the interaction between hypoxia and STAT3 signaling in the osteogenic differentiation of precursor cells during bone defect healing is still unknown. METHODS: In this study, we assessed the impact of different durations of CoCl2-induced cellular hypoxia on the osteogenic differentiation of MSCs. Role of STAT3 signaling on hypoxia induced osteogenic differentiation was analyzed both in vitro and in vivo. The interaction between cellular hypoxia and STAT3 signaling in vivo was investigated in a mouse femoral bone defect model. RESULTS: The peak osteogenic differentiation and expression of vascular endothelial growth factor (VEGF) occurred after 3 days of hypoxia. Inhibiting STAT3 reversed this effect. Hypoxia enhanced the expression of hypoxia-inducible factor 1-alpha (HIF-1α) and STAT3 phosphorylation in MSCs. Histology and µ-CT results showed that CoCl2 treatment enhanced bone defect healing. Inhibiting STAT3 reduced this effect. Immunohistochemistry results showed that CoCl2 treatment enhanced Hif-1α, ALP and pSTAT3 expression in cells present in the bone defect area and that inhibiting STAT3 reduced this effect. CONCLUSIONS: The in vitro study revealed that the duration of hypoxia is crucial for osteogenic differentiation of precursor cells. The results from both the in vitro and in vivo studies show the role of STAT3 signaling in hypoxia-induced osteogenic differentiation of precursor cells and bone defect healing.

Using a Modified Postauricular Hemicoronal Incision to Manage Unilateral Zygomaticomaxillary Complex Fracture.

BACKGROUND: The surgical approach of the zygomaticomaxillary complex fracture is usually performed with preauricular coronal incision assisted with intraoral maxillary sulcus incision. There will be preauricular scars postoperatively. METHODS: The authors introduce a postauricular hemicoronal incision to avoid the formation of scars in front of the ear. RESULTS AND DISCUSSION: The postauricular hemicoronal incision can avoid vascular damage caused by careless operation in the preauricular approach. It eliminates the possibility of dissection or ligation of the superficial arteries and veins when preauricular approach was used. It results in no scar in front of ear, while reducing suture time and complexity.

Effects of connective tissue growth factor (CTGF/CCN2) on condylar chondrocyte proliferation, migration, maturation, differentiation and signalling pathway.

CCN2, also known as connective tissue growth factor (CTGF), is a 38 kDa cysteine-rich extracellular matrix protein that regulates a sequence of cellular functions and participates in multiple complex biological processes, such as chondrogenesis and osteogenesis. In the present study, we provided the first evidence describing the physiological role of CCN2 in condylar chondrocyte proliferation, migration, maturation and differentiation. CCN2 was widely expressed throughout the whole layers of condylar cartilage and predominantly distributed in the proliferative zone. Recombinant CCN2 promoted the proliferation, migration, proteoglycan synthesis and differentiation capacity of isolated condylar chondrocytes. The stimulatory effect of CCN2 on chondrocyte proliferation was associated with the activation of phosphatidylinositol 3-kinase/Akt signalling pathway. The blocking of this pathway by its inhibitor LY294002 impaired the proliferative effect of CCN2 on chondrocytes. These results suggested a novel physiological role of CCN2 in the development of condylar cartilage.

Inhibition of JAK2/STAT3 signaling suppresses bone marrow stromal cells proliferation and osteogenic differentiation, and impairs bone defect healing.

Mesenchymal stem cells (MSCs) undergo osteogenic differentiation during bone defect healing. However, the role of JAK2/STAT3 in the osteogenic differentiation of MSCs and bone defect healing is still not fully understood. In this study, we aimed to analyze the effect of AG490, a JAK2-specific inhibitor, on MSCs proliferation and osteogenic differentiation as well as in bone defect healing. We used AG490 to inhibit the JAK2/STAT3 signaling in a mice bone marrow stromal cells (BMSCs) culture. AG490 inhibited BMSCs proliferation and osteogenic differentiation markers, i.e. Col1α, Alp and Ocn expression in mRNA and protein levels. Inhibition of JAK2 reduced ALP activity and matrix mineralization in BMSCs culture. Inhibition of JAK2 reduced phosphorylation of STAT3, AKT, P38, and JNK phosphorylation. Immunohistochemistry showed high numbers of pJAK2, pSTAT3 and ALP positive cells and AG490 reduced this effect in vivo. Histology and µ-computed tomography (CT) data showed that AG490 treatment inhibits bone regeneration and bone defect healing. Our results clearly showed the inhibitory effect of AG490 on proliferation and osteogenic differentiation of BMSCs, bone regeneration and bone defect healing. Moreover, AG490 inhibited phosphorylation of STAT3, P38, JNK and AKT. This suggests the possible role of JAK2/STAT3 signaling in hypoxia-induced osteogenic differentiation of MSCs and bone defect healing.

CoCl2 , a mimic of hypoxia, enhances bone marrow mesenchymal stem cells migration and osteogenic differentiation via STAT3 signaling pathway.

Mesenchymal stem cells homing and migration is a crucial step during bone fracture healing. Hypoxic environment in fracture site induces bone marrow mesenchymal stem cells (BMSCs) migration, but its mechanism remains unclear. Our previous study and studies by other groups have reported the involvement of signal transducer and activator of transcription 3 (STAT3) pathway in cell migration. However, the role of STAT3 pathway in hypoxia-induced cell migration is still unknown. In this study, we investigated the role of STAT3 signaling in hypoxia-induced BMSCs migration and osteogenic differentiation. BMSCs isolated from C57BL/6 male mice were cultured in the presence of cobalt chloride (CoCl2 ) to simulate intracellular hypoxia. Hypoxia enhanced BMSCs migration, and upregulated cell migration related gene expression, that is, metalloproteinase (MMP) 7, MMP9, and C-X-C motif chemokine receptor 4. Hypoxia enhanced the phosphorylation of STAT3, and cell migration related proteins: c-jun n-terminal kinase (JNK), focal of adhesion kinase (FAK), extracellular regulated protein kinases, and protein kinase B 1/2 (ERK1/2). Moreover, hypoxia enhanced expression of osteogenic differentiation marker. Inhibition of STAT3 suppressed the hypoxia-induced BMSCs migration, cell migration related signaling molecules phosphorylation, and osteogenic differentiation related gene expression. In conclusion, our result indicates that hypoxia-induced BMSCs migration and osteogenic differentiation is via STAT3 phosphorylation and involves the cooperative activity of the JNK, FAK, and MMP9 signaling pathways.

Treatment of Sagittal Fracture of the Zygomatic Arch Root Assisted by Surgical Navigation Technology.

Sagittal fracture at the temporal root of the zygomatic arch often occurs as a part of zygomaticomaxillary fractures. The authors described the application of computer-assisted navigation in the lag screw insertion for the fixation of sagittal fracture at the temporal root of zygomatic arch. Using the presurgical planning of the computer-assisted navigation system, the trajectory of lag screw insertion was designed, and the insertion depth was calculated. In the presurgical planning, the trajectory of screw insertion was placed with an anterior inclination of 10° to 15° (mean: 12.24°), and the screw insertion depth was 9.0 to 12.0 mm (mean: 10.65 mm). In the operation, the screw insertion in the fixation of the sagittal fracture was performed under the guidance of navigation system according to the presurgical planning. The postoperative CT scan showed exact reduction and fixation of the sagittal fracture in all cases. Computer-assisted navigation is a useful tool for the lag screw insertion in the precise fixation of sagittal fracture at the temporal root of the zygomatic arch in complex zygomaticomaxillary fractures.

AG490 suppresses interleukin-34-mediated osteoclastogenesis in mice bone marrow macrophages.

Interleukin-34 (IL-34) has been recently identified as a novel cytokine, substituting for the function of macrophage colony-stimulating factor (M-CSF), a pivotal osteoclastogenic factor involved in bone-related diseases (e.g., osteomyelitis of the jaws). However, the molecular mechanisms are not fully understood. This study aimed to explore the potential mechanism of IL-34 in receptor activator of NF-kB ligand (RANKL)-induced osteoclast formation. We found that IL-34 alone significantly maintained the survival of bone marrow macrophages (BMMs) and enhanced the expression of the osteoclast-related genes TRAP, Ctsk, and NFATc1, as well as TRAP-positive multinucleated cells combined with RANKL, which can be reversed by AG490. Conversely, AG490 did not affect the M-CSF-mediated osteoclastogenesis in the presence of RANKL. The protein expression of p-STAT3 in BMMs was enhanced by IL-34 combined with RANKL compared with RANKL alone, and AG490 inhibited the expression of p-SATA3 at protein level in the IL-34 plus RANKL group, resulting in significantly increased Smad7 expression. This study demonstrated for the first time that IL-34 may play a crucial role in RANKL-induced osteoclastogenesis by promoting the proliferation and differentiation of BMMs, stimulating p-STAT3 expression, and inhibiting the expression of Smad7 in the absence of M-CSF.