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ABSTRACT: Recently, a cohort of miRNAs, including miR-31, was reported to be down-regulated during osteogenic induction by miR microarray analysis. It remains unclear how changes in miR-31 expression collaborate with bone transcription factors to activate the biological pathways that regulate the differentiation of bone mesenchymal stem cells (BMSCs). Here, the effects of miR-31, Runx2 and Satb2 on the osteogenic differentiation of BMSCs were investigated using mimics and inhibitors of miR-31, small interfering RNA for knockdown of Runx2 and plasmids for over-expression of Runx2. Our results showed that miR-31 expression decreased progressively in BMSC cultures during differentiation. Inhibition of miR-31 dramatically increased ALP activity and mineralization in BMSC cultures. Additionally, miR-31 diminished the levels of Satb2 protein without significantly affecting Satb2 mRNA levels, and Runx2 directly repressed miR-31 expression. Over-expression of miR-31 significantly reduced expression of the osteogenic transcription factors OPN, BSP, OSX and OCN, but not Runx2. Furthermore, the high expression of miR-31 in BMSCs cultured in proliferation medium repressed Satb2 protein levels, which may contribute to the maintenance of BMSCs in an undifferentiated state. In conclusion, our results suggest that a Runx2, Satb2 and miR-31 regulatory mechanism may play an important role in inducing BMSC osteogenic differentiation. The results of this study provide us with a better understanding of the molecular mechanisms that govern BMSC cell fate.
Stem cells and development 03/2013; · 4.15 Impact Factor
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ABSTRACT: Thyroid-associated ophthalmopathy (TAO) is characterised by increased volume of the orbital contents involving adipose tissue, but the factors responsible for stimulation of orbital adipogenesis remain uncertain. Previous studies have shown that insulin-like growth factor 1 (IGF-1) is increased in the orbital fatty connective tissues of patients with TAO. The present study was conducted to investigate the effects of IGF-1 on orbital adipose-derived stromal cells (OADSCs) derived from TAO patients and to identify the signalling mechanisms involved. Our results showed that IGF-1 significantly promoted the cell proliferation and lipid accumulation of TAO OADSCs. The mRNA expression of adipogenic markers (adiponectin, leptin, adipocyte fatty acid binding protein [AP2] and fatty acid synthase [FAS]) was increased in TAO cultures treated with IGF-1. Further research demonstrated that the protein levels of peroxisome proliferator-activated receptor-γ (PPARγ) were up-regulated when OADSCs were treated with IGF-1. We also found that the inhibition of either IGF-1 receptor (IGF-1R) or phosphoinositide 3-kinase (PI3K) activity decreased the levels of IGF-1-stimulated mRNA encoding adiponectin, leptin, AP2, and FAS, as well as PPARγ protein levels. Moreover, the expression of phosphorylated Akt (p-Akt) protein in TAO cells was up-regulated by IGF-1, while a specific PI3K inhibitor (LY294002) or an antibody of IGF-1R blocked this effect. These results indicate that IGF-1 is a pro-proliferative and pro-adipogenic factor in TAO OADSCs. IGF-1 enhances the adipogenesis of TAO OADSCs by up-regulation of PPARγ via the activation of the IGF-1R and PI3K pathways, suggesting that the blocking of IGF-1R or inhibition of PI3K signalling might be a potential novel therapeutic approach to TAO.
Experimental Eye Research 12/2012; · 3.26 Impact Factor
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ABSTRACT: PURPOSE: With the increasing number of patients with facial trauma, orbital-zygomatic-maxillary (OZM) fracture combined with orbital wall fracture has become common. Such fractures always induce symptoms of enophthalmos, hypoglobus, and diplopia. This study was aimed to investigate the surgical technique and operative effect of late reconstruction of OZM fractures combined with orbital wall fractures. METHODS: A retrospective analysis of the 46 patients (46 orbits) who were treated from January 2005 to December 2008 was performed. All cases had reconstruction of OZM fractures combined with orbital wall fractures at an average of 5.3 months after injury. Various incisions were selected. According to the computer-aided design/computer-aided manufacturing design, the osteotomy, reposition, and 4-point fixation of the fractured bones were individualized performed. Titanium mesh was preshaped according to the mirroring technology and inserted into the orbit with or without high-density polyethylene (HDPE) implant material to repair the orbital wall defect and the enlarged orbital volume. All patients were followed up 1 year after surgery. RESULTS: Forty-two of the 46 patients who had enophthalmos were completely corrected. Forty patients who had hypoglobus were corrected postoperatively. Of the 43 cases with diplopia, 20 cases were resolved. CONCLUSIONS: Late reconstruction by osteotomy and 4-point fixation could recover midface cosmesis, correct the enophthalmos, and improve the diplopia of OZM fractures combined with orbital wall fractures. The computer-aided design/computer-aided manufacturing system and mirroring technology can help improve the outcome of surgery when repairing such fractures.
The Journal of craniofacial surgery 11/2012; · 0.81 Impact Factor
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ABSTRACT: Mesenchymal stem cells (MSCs) are attractive candidates for cell therapy and regenerative medicine because of their potential for proliferation and multilineage differentiation. MSCs secrete various cytokines, acting as trophic mediators to regulate neighboring cells. Osteoblasts are the cells directly responsible for forming new bone, and they are the final target of many osteogenic regulators. However, the induction effect of MSCs on osteoblasts is still unknown. In this study, we isolated osteoblasts from rat calvariae and investigated their proliferation and differentiation under induction of varied concentrations of MSC-conditioned medium (MSC-CM). Cells in the MSC-CM groups showed a reduction in cell proliferation at 3-6 days, and a decrease in the expression of osteocalcin and osteopontin at 3 days, with low levels of alkaline phosphatase activity. The expression of osteogenic markers went back to normal at 7 days. In order to evaluate the molecular mechanisms underlying this suppression, levels of two osteoblastic transcription factors, runt-related transcription factor 2 (Runx2) and osterix (Osx), were detected at both mRNA and protein levels. The results indicated that MSC-CM significantly inhibited Runx2 expression in a concentration-dependent manner. However, the effect was not due to the inhibition of Osx, for Osx was not significantly altered. This work demonstrates that MSCs may suppress osteoblast proliferation and transiently retard osteoblast differentiation by downregulating Runx2. These results highlight the need to take into account the paracrine effect of MSCs when using them in regenerative medicine for the repair of bone defects.
Cells Tissues Organs 08/2012; · 2.20 Impact Factor
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ABSTRACT: Orbital implant-associated complications always affect patients, resulting in multiple operations. One-stage replacement of complicated implants has been attractive for reducing operation times and preventing long-time appearance without artificial eye. We retrospectively analyzed the outcomes of 1-stage replacement surgery of orbital implant. A total of 21 eyes in 21 cases with noninfectious complications, who failed conservative therapies and surgical repairs, were treated with 1-stage orbital implant replacement. After a detailed ophthalmic history was obtained and examinations performed, patients with apparent purulent secretion in conjunctival sac were excluded. The preexisting orbital implant was carefully removed, and a new hydroxyapatite sphere was implanted simultaneously. Wound healing status, prosthesis movement, and cosmetic features were evaluated and recorded after at least 6 months' follow-up. Orbital implant exposure(16 cases) was the main indication of the replacement surgery; other causes included superior orbital area depression (2 cases), conjunctival fistula (1 case), orbital implant malposition (1 case), and the metal material of implant obstructing magnetic resonance imaging scan in 1 case. Eye-socket hollow was redressed in all cases immediately, and 95.23% cases (20/21) could wear an artificial eye and had a good cosmetic appearance, whereas conjunctival sac fistula reoccurred in 1 patient, and the implant was removed ultimately. Conjunctival sac constrictions occurred in 4 cases after operation and were treated by secondary conjunctival sac reconstruction 6 months later. In conclusion, 1-stage replacement of orbital implants offers an effective and efficient strategy for dealing with severe postimplantation noninfectious complications in achieving a symmetrically cosmetic appearance without delay.
The Journal of craniofacial surgery 03/2012; 23(2):e146-9. · 0.81 Impact Factor
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ABSTRACT: Laser canaliculoplasty is widely used to treat lacrimal duct obstruction. We describe 12 patients in whom eyelid lipogranuloma developed subsequent to laser canaliculoplasty, followed by tobramycin and dexamethasone, ofloxacin, or erythromycin ointment injected in the lacrimal duct.
Clinical history, ocular workup, and CT were performed. Histopathologic examination was performed after eyelid tissue excision.
Over a period of 3 years, 12 patients were diagnosed with eyelid lipogranuloma caused by diffusion and deposition of ointment. Seven of 12 patients were injected with tobramycin and dexamethasone ointment, 3 patients were injected with ofloxacin ointment, and 2 patients were injected with erythromycin ointment. Histopathologic features of the excised tissue included multifocal spaces surrounded by multinucleated giant cells, considered to be lipogranulomatous inflammation.
The incidence of lipogranuloma caused by transcanalicular ointment injection after laser canaliculoplasty is low. Surgical excision of the lipogranuloma should be performed only when it becomes relatively localized and has passed the acute phase of inflammation to avoid the recurrence of lipogranuloma and diffusion of the inflammation. A cosmetic outcome should be considered, and simultaneous blepharoplasty with transplantation of herniated fat pads may be performed in either or both eyelids to achieve a satisfactory appearance. Injection of ointment in the lacrimal duct should be avoided, as it might create unnecessary complications when a new channel is created or when canalicular walls are penetrated. Local massage after ointment injection is not recommended.
Ophthalmic plastic and reconstructive surgery 05/2011; 27(5):333-7. · 0.69 Impact Factor
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ABSTRACT: Retinoblastoma is a common malignant intraocular tumor in childhood, and most patients require enucleation or exenteration even with irradiation. Severe anophthalmic orbits and atresic eye sockets are not rare. We conducted a retrospective study to evaluate the results of surgical management of reconstruction of severe anophthalmic orbits and atresic eye sockets with vascular anastomosed free dorsalis pedis flap transplantation. There were 5 patients (5 eyes) who underwent reconstructive surgery of severe anophthalmic orbits and atresic eye sockets after enucleation and irradiation of retinoblastoma in our hospital during the 3 years. All patients had enucleation and irradiation immediately after the retinoblastoma was diagnosed and had never worn artificial eyes because of the atresic eye sockets. Vascular anastomosed free dorsalis pedis flaps, whose dimensions were typically 6.5 × 5.5 cm(2), were transplanted to reconstruct the severe anophthalmic orbits and atresic eye sockets. The donor sites were covered by free abdominal skin flaps. All the vascular anastomosed free dorsalis pedis flaps were valid after more than 6 months of follow-up. And then all the 5 patients underwent secondary autogenous dermal fat implantation to augment the supraorbital area depression. After the 2-stage reconstruction surgery, the dimensions of the eye sockets were adequate, and all patients were able to wear their prosthesis and had a satisfactory cosmetic result. Implantation of alloplastic materials is not recommended because of insufficient blood supply of the irradiated orbital area.
The Journal of craniofacial surgery 05/2011; 22(3):792-6. · 0.81 Impact Factor
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ABSTRACT: Most of the patients who undergo double-eyelid blepharoplasty report satisfactory cosmetic results. However, it remains some complications such as the failure to create double-eyelid skin creases and the outcome of higher skin creases and asymmetrical upper eyelids. These complications may happen even when the surgery proceeded successfully and the septum was intact, which suggested that the aponeurosis could not been damaged. Between January 2008 and June 2009, 39 patients (51 eyes, 7.75%) who requested double-eyelid blepharoplasty were found to display 'latent' aponeurotic ptosis. In these patients, the aponeuroses were disinserted from the tarsus or attenuated and elongated. All of these patients agreed to undergo aponeurotic ptosis correction along with double-eyelid surgery, of which 34 (45 eyes, 88.24%) were deemed successful. We believe that the careful measurement of ptosis in cosmetic patients will help to identify patients with 'latent' aponeurotic ptosis. Incorporation of the aponeurotic reinsertion and minimal dissection into the blepharoptosis surgery will correct the 'latent' aponeurotic ptosis successfully.
Journal of Plastic Reconstructive & Aesthetic Surgery 04/2011; 64(8):993-9. · 1.49 Impact Factor
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ABSTRACT: Bone graft substitutes with osteogenic factors alone often exhibit poor bone regeneration due to inadequate vascularization. Combined delivery of osteogenic and angiogenic factors from biodegradable scaffolds may enhance bone regeneration. We evaluated the effects of bone morphogenetic protein 2 (BMP2) and vascular endothelial growth factor (VEGF), combined with natural coral scaffolds, on the repair of critical-sized bone defects in rabbit orbits. In vitro expanded rabbit bone marrow stromal cells (BMSCs) were transfected with human BMP2 and VEGF165 genes. Target protein expression and osteogenic differentiation were confirmed after gene transduction. Rabbit orbital defects were treated with a coral scaffold loaded with BMP2-transduced and VEGF-transduced BMSCs, BMP2-expressing BMSCs, VEGF-expressing BMSCs, or BMSCs without gene transduction. Volume and density of regenerated bone were determined by micro-computed tomography at 4, 8, and 16 weeks after implantation. Neovascularity, new bone deposition rate, and new bone formation were measured by immunostaining, tetracycline and calcein labelling, and histomorphometric analysis at different time points. The results showed that VEGF increased blood vessel formation relative to groups without VEGF. Combined delivery of BMP2 and VEGF increased new bone deposition and formation, compared with any single factor. These findings indicate that mimicking the natural bone development process by combined BMP2 and VEGF delivery improves healing of critical-sized orbital defects in rabbits.
Biomedical Materials 02/2011; 6(1):015013. · 2.16 Impact Factor
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Journal of oral and maxillofacial surgery: official journal of the American Association of Oral and Maxillofacial Surgeons 12/2010; 69(6):1736-9. · 1.58 Impact Factor
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ABSTRACT: The three-dimensional (3D) reconstruction technique serves as a practical tool in diagnosis, surgical planning, and outcome prediction of plastic and reconstructive surgery. In our study, the morphologic features of the Chinese adult orbit were described by 11 anatomic parameters using a 3D reconstruction technique. Sixty-four Chinese adults were selected randomly from patients who had undergone craniofacial computed tomography (CT) scans to diagnose conditions other than craniofacial or orbital deformations. The morphologic parameters of orbit such as bony orbital volume, orbital foramen area and orbital rim perimeter were measured on 3D models using this technique. Differences between the two orbits and between the two sexes were investigated. The method of measurement showed high reproducibility of results. No difference between the two orbits was found. There were significant differences between men and women in all anatomic parameters other than orbital height. In men and women, respectively, mean bony orbital volume was 26.02 and 23.32 mL, mean orbital foramen area 11.80 and 11.10 cm², mean orbital rim perimeter 12.65 and 12.20 cm, mean orbital height 33.35 and 33.22 mm, mean orbital width 40.02 and 38.00 mm; mean orbital floor length 47.93 and 46.18 mm, mean orbital roof length 52.93 and 50.89 mm, mean medial orbital wall length 46.43 and 44.41 mm, mean lateral orbital wall length 48.38 and 46.91 mm, mean intraorbital distance 27.18 and 25.11 mm, mean extra-orbital distance 98.77 and 93.69 mm. It is concluded that the measurements of these orbital parameters could be obtained from a 3D reconstruction method. The two orbits were symmetric based on orbital volume and other anatomic parameters. Orbital size was significantly smaller in women than in men; orbital height, however, was similar. The findings of the present study allow for quantification of the orbital features of Chinese adults and provide parameters for preoperative planning and prediction of postoperative outcome.
Journal of Anatomy 11/2010; 217(5):501-6. · 2.37 Impact Factor
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ABSTRACT: To repair the segmental orbital rim defects of dogs with three-dimensional (3D) tissue-engineered constructs derived from culturing autogenous bone marrow stromal cells (BMSCs) on β-tricalcium phosphate (β-TCP) scaffolds.
A 25-mm segmental defect on the canine inferior orbital rim was created. BMSCs were isolated and osteogenically induced in vitro, then were seeded onto 3D β-TCP scaffolds and implanted to repair the orbital defects after 5 days of cultivation. The group of noninduced BMSC/β-TCP, β-TCP alone, and the normal inferior orbital rim were set as controls. The orbits of all groups had spiral computed tomography (CT) scans 1, 4, 8, and 12 weeks after surgery. Gross examination, bone density, microCT, and histologic measurements were performed 12 weeks after surgery. The results were analyzed to evaluate the extent of bone repair.
Twelve weeks after surgery, CT examination revealed good inferior orbital rim recovery in the induced BMSC/β-TCP group, and the bone density was 0.30 ± 0.03 g/cm(2) with no dominant variance, compared with the normal control (P > 0.05). MicroCT and histologic examination confirmed that the implantations led to good repair of the defects. Pore-like spongy bone surrounded the implants through the section plane, with some residue remaining in the center. In contrast, the noninduced BMSC/β-TCP implants were not fully repaired, and nonunion was evident. The bony density for this group was 0.23 ± 0.07 g/cm(2), which was significantly lower than that of the control group (P < 0.05). The β-TCP group was largely held by fibrous tissues.
Engineered bone from induced BMSCs and 3D biodegradable β-TCP can efficiently repair critical-sized segmental orbital defects in dogs.
Investigative ophthalmology & visual science 11/2010; 52(3):1735-41. · 3.43 Impact Factor
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ABSTRACT: Repair of orbital bone defects caused by trauma, infection or cancer is a continuous challenge in reconstructive surgery. Few studies have reported the application of tissue engineering for the repair of orbital bone defects in large animal models. Thus, we investigated the effects of tissue-engineered bone enhanced by the human bone morphogenetic protein-2 (BMP2) on the repair of orbital wall defects in a canine model. Autologous bone marrow stromal cells (BMSCs) from 16 Beagle dogs were isolated and cultured in vitro. Passage 2 cells were transfected with adenovirus containing human BMP2 (adv-BMP2) and tissue-engineered bone was constructed using BMP2-expressing BMSCs seeded on a biocoral scaffold. Circular defects (12-mm diameter) created bilaterally in the canine medial orbital wall, were treated with one of the following: adv-BMP2-transfected BMSC/coral composite (group I, n=8), BMSC/coral composite (group II, n=8), biocoral alone (group III, n=8), or were left untreated (group IV, n=8). Four samples from each group were harvested at 12 and 24 weeks after surgery, and the volume and density of newly regenerated bone were determined by micro-computed tomographic (micro-CT) measurement. The rate of new bone deposition and regeneration was measured by tetracycline/calcein labeling and histomorphometric analysis. The results showed that a canine 12-mm circular orbital defect was a critical-sized defect, and the micro-CT and histomorphometry detection results indicated that the combined delivery of BMSCs and BMP2 (group I) resulted in the highest regenerative effects on orbital bone defects, compared to the other groups without BMP2. Biocoral scaffolds combined with BMSCs enhanced by BMP2 could improve the healing of critical-sized medial orbital wall defects in canines.
International Journal of Molecular Medicine 10/2010; 26(4):517-25. · 1.98 Impact Factor
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ABSTRACT: To present the clinical manifestations and outcome of the surgical management of subjects with Tessier number 10 clefts.
Retrospective, interventional case series.
Twelve patients with Tessier number 10 clefts treated at the Department of Ophthalmology of Shanghai Ninth People's Hospital between January of 2002 and December of 2005.
All 12 patients (15 eyes) underwent a standard ophthalmologic assessment, and the orbits were examined by a 3-dimensional computed tomography scan. Reconstructive techniques included eyebrow reconstruction with a frontal hairline transposition flap, eyelid reconstruction with a hard palate mucosa-lined sliding myocutaneous flap, and conjunctival fornix reconfiguration using a mucous membrane graft. In patients requiring enucleation, hydroxyapatite implant was used, followed by fitting of ocular prosthesis.
Postoperative upper eyelid and eyebrow contour and viability, recurrence of symblepharon, and ability to hold prosthesis.
All reconstructed eyelids achieved the surgical goal of providing corneal coverage and the ability to hold a cosmetic contact lens or an ocular prosthesis. Eyebrow reconstruction was performed in 4 patients. The reconstructed eyebrow was symmetrical with the opposite side. There was no recurrence of symblepharon. Three patients wore cosmetic contact lenses, and their eyelid function appeared adequate. Two patients underwent enucleation along with insertion of a hydroxyapatite implant, followed by fitting of ocular prosthesis.
The surgical approach described in our series of cases seems to be effective in repairing Tessier number 10 clefts. Eyebrow reconstruction with a frontal hairline transposition flap followed by eyelid repair with a hard palate mucosa-lined sliding myocutaneous flap is a suitable technique for correcting eyebrow and eyelid malformations in adults.
The authors have no proprietary or commercial interest in any materials discussed in this article.
Ophthalmology 07/2008; 115(12):2290-2294.e3. · 5.45 Impact Factor
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ABSTRACT: This study measured direct orbital tension (DOT) in normal and fractured orbits of Chinese patients before and after orbital fracture repair, to investigate the changes in DOT and intraocular pressure (IOP) after surgery and to evaluate any correlation between them.
DOT was directly measured by a specially designed orbitonometer before and after orbital fracture surgery in 40 cases of unilateral orbital fractures, using the contralateral eyes as a control group. All of the patients were submitted to orbital fracture repair and globe repositioning. IOP and ocular function were recorded preoperatively and postoperatively.
DOT was 5.0 +/- 1.3 mm Hg (mean +/- SD) in the normal orbits. DOT was positively correlated with IOP (r = 0.56; P < .01). DOT and IOP were significantly decreased (s = 81, P = .01 and s = 49.5, P = .02, respectively) on the fractured orbit side. Postoperative DOT and IOP were significantly increased (s = 410, P < .01 and s = 390, P < .01, respectively). The preoperative to postoperative changes in both DOT and IOP were positively correlated (r = 0.54; P < .01).
DOT can be measured safely using an orbital manometer in normal and fractured orbits. DOT and IOP increased significantly after orbital fracture surgery. DOT was well-correlated with IOP both preoperatively and postoperatively.
Journal of Oral and Maxillofacial Surgery 11/2007; 65(11):2282-7. · 1.64 Impact Factor
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ABSTRACT: To construct three-dimensional (3D) imaging and computer generated models of complex orbital fractures, and develop a Computer-Aided Design/Computer-Aided Manufacture (CAD/CAM) system to help improve the surgical planning of complex orbital fracture and promote its outcome.
A prospective study was carried out on 17 patients with unilateral complex orbital fractures from Mar 2003 to Mar 2006 at the Shanghai ninth people's hospital. The utilization of a CAD/CAM technique based on Helical computer tomography data, with stereolithographical (SLA) modelling as intermediate step, enabled surgeons to plan for the surgical progress of osteotomy, movement, reposition, fixation and material implanting. Orbital volume was calculated pre and post-operatively. Orbital fracture reconstruction and globe repositioning was performed and followed up 3-9 months post-treatment. Ocular function and aesthetic deformities such as enophthalmos, diplopia and extraocular motility problems were accessed. The data was processed with SAS 6.17 statistical software.
17 patients with complex orbital fractures underwent successful orbital fracture reconstruction surgery. The deformities of orbit, medial canthus, nose, zygomata, maxillary and frontal bone were well corrected. The volume of reconstructed orbit was approximately symmetrical with respect to the contralateral orbit. Enophthalmos was corrected and diplopia, extraocular movement were improved.
CAD/CAM system enables the surgeon to predict reconstructive surgical steps before the operation, and can help to improve the outcome of surgery. This technique may be proved as one of the most useful clinical tools for orbital surgery.
Journal of Craniofacial Surgery 06/2007; 18(3):665-73. · 0.82 Impact Factor
