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1.
Plast Reconstr Surg Glob Open ; 7(9): e2388, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31741810

ABSTRACT

Bony ankylosis of the temporomandibular joints (TMJ) occurs in up to 28% of patients with syndromic mandibular dysostoses. Release of complete osseous ankylosis is particularly challenging due to the lack of tissue planes separating the mandible from the skull base and the presence of congenital skeletal abnormalities. One recent advance in surgical imaging technology is three-dimensional virtual reality (3D VR), now in common use in neurosurgical resections. In this study, we describe the usage of 3D VR in TMJ arthroplasty and compare 3D VR to traditional computed tomographic (CT) guidance. Pediatric patients with syndromic mandibular micrognathia including Treacher Collins, Nager, and cerebrocostomandibular syndrome were retrospectively evaluated between 2008 and 2016. Patient characteristics, complications, inpatient times, and operative times were recorded. Of the 29 children with syndromic mandibular micrognathia treated between 2008 and 2016, 7 were diagnosed with TMJ ankyloses. Four consecutive pediatric patients (mean 8.7 years) undergoing interpositional TMJ arthroplasty with Matthews device placement were retrospectively evaluated. Two patients underwent traditional CT-guided versus 3D VR-guided temporomandibular joint arthroplasty (TMJA). No statistically significant differences were found among the age, complications, or inpatient hospitalization times. The average operative time in the traditional CT guidance group was 300 minute versus 134 minutes in the 3D VR group. Three-dimensional VR is a useful preoperative planning and intraoperative guidance tool. The major difference between VR and older technologies is the improved imaging in 3 dimensions for guidance, thereby potentially decreasing operative times.

3.
Plast Reconstr Surg Glob Open ; 6(6): e1825, 2018 Jun.
Article in English | MEDLINE | ID: mdl-30276052

ABSTRACT

BACKGROUND: Widespread application of vascularized composite allotransplantation (VCA) is currently limited by the required lifelong systemic immunosuppression and its associated morbidity and mortality. This study evaluated the efficacy of ex vivo (after procurement but before transplantation) engineering of allografts using small interfering RNA to knockdown major histocompatibility complex I (MHC-I) and prolong rejection-free survival. METHODS: Endothelial cells (ECs) were transfected with small interfering RNA targeted against MHC-I (siMHC-I) for all in vitro experiments. MHC-I surface expression and knockdown duration were evaluated using quantitative polymerase chain reaction (qPCR) and flow cytometry. After stimulating Lewis recipient cytotoxic lymphocytes (CTL) with allogeneic controls or siMHC-I-silenced ECs, lymphocyte proliferation, CTL-mediated and natural killer-mediated EC lysis were measured. Using an established VCA rat model, allografts were perfused ex vivo with siMHC-I before transplantation. Allografts were analyzed for MHC-I expression and clinical/histologic evidence of rejection. RESULTS: Treatment with siMHC-I resulted in 80% knockdown of mRNA and 87% reduction in cell surface expression for up to 7 days in vitro (P < 0.05). Treatment of ECs with siMHC-I reduced lymphocyte proliferation and CTL-mediated cytotoxicity (77% and 50%, respectively, P < 0.01), without increasing natural killer-mediated cytotoxicity (P = 0.66). In a rat VCA model, ex vivo perfusion with siMHC-I reduced expression in all tissue compartments by at least 50% (P < 0.05). Knockdown prolonged rejection-free survival by 60% compared with nonsense-treated controls (P < 0.05). CONCLUSIONS: Ex vivo siMHC-I engineering can effectively modify allografts and significantly prolong rejection-free allograft survival. This novel approach may help reduce future systemic immunosuppression requirements in VCA recipients.

4.
Article in English | MEDLINE | ID: mdl-27331195

ABSTRACT

Strategies in skeletal regeneration research have been primarily focused on optimization of three components: cellular progenitors, biomaterials, and growth factors. With the increased understanding that circulating progenitor cells exist in peripheral blood, the question arises whether such cell types would allow for adequate osteogenesis and mineralization. In this review, we discuss the current literature on circulating progenitor cells in in vitro and in vivo studies on bone regeneration.

5.
Plast Reconstr Surg ; 137(4): 1151-1156, 2016 Apr.
Article in English | MEDLINE | ID: mdl-27018670

ABSTRACT

BACKGROUND: Augmentation gluteoplasty has been performed more frequently in the past decade, with over 21,000 procedures performed in the past year alone. The most popular methods for buttock augmentation involve silicone prostheses and autologous fat grafting. A comparison of complications of these two techniques does not exist in our literature. METHODS: The PubMed, MEDLINE, and Cochrane databases were searched through April of 2015 for studies that achieved buttock augmentation through the use of silicone implant placement or autologous lipoinjection. Complication outcomes of interest included wound dehiscence, infection, seroma, hematoma, asymmetry, and capsular contracture. RESULTS: Forty-four articles met inclusion criteria. The most commonly reported complications in 2375 patients receiving silicone implants were wound dehiscence (9.6 percent), seroma (4.6 percent), infection (1.9 percent), and transient sciatic paresthesias (1.0 percent), with an overall complication rate of 21.6 percent (n = 512). The most commonly reported complications in 3567 patients receiving autologous fat injection were seroma (3.5 percent), undercorrection (2.2 percent), infection (2.0 percent), and pain or sciatalgia (1.7 percent), with an overall complication rate of 9.9 percent (n = 353). Patient satisfaction after surgery was assessed differently among studies and could not be compared quantitatively. CONCLUSIONS: Although gluteal augmentation was once reported to have complication rates as high as 38.1 percent, a systematic review of the two most popular techniques demonstrated substantially lower overall complication rates. The overall complication rate with autologous fat grafting (9.9 percent) is lower than that with silicone buttock implants (21.6 percent). A standardized method of measuring patient satisfaction is necessary to fully understand outcomes of these increasingly popular procedures.


Subject(s)
Buttocks/surgery , Cosmetic Techniques , Cosmetic Techniques/adverse effects , Cosmetic Techniques/instrumentation , Humans , Outcome Assessment, Health Care , Postoperative Complications
6.
Diabetes ; 65(3): 633-46, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26647385

ABSTRACT

Chronic hyperglycemia impairs intracellular redox homeostasis and contributes to impaired diabetic tissue regeneration. The Keap1/Nrf2 pathway is a critical regulator of the endogenous antioxidant response system, and its dysfunction has been implicated in numerous pathologies. Here we characterize the effect of chronic hyperglycemia on Nrf2 signaling within a diabetic cutaneous regeneration model. We characterized the effects of chronic hyperglycemia on the Keap1/Nrf2 pathway within models of diabetic cutaneous wound regeneration. We assessed reactive oxygen species (ROS) production and antioxidant gene expression following alterations in the Nrf2 suppressor Keap1 and the subsequent changes in Nrf2 signaling. We also developed a topical small interfering RNA (siRNA)-based therapy to restore redox homeostasis within diabetic wounds. Western blotting demonstrated that chronic hyperglycemia-associated oxidative stress inhibits nuclear translocation of Nrf2 and impairs activation of antioxidant genes, thus contributing to ROS accumulation. Keap1 inhibition increased Nrf2 nuclear translocation, increased antioxidant gene expression, and reduced ROS production to normoglycemic levels, both in vitro and in vivo. Topical siKeap1 therapy resulted in improved regenerative capacity of diabetic wounds and accelerated closure. We report that chronic hyperglycemia weakens the endogenous antioxidant response, and the consequences of this defect are manifested by intracellular redox dysregulation, which can be restored by Keap1 inhibition. Targeted siRNA-based therapy represents a novel, efficacious strategy to reestablish redox homeostasis and accelerate diabetic cutaneous tissue regeneration.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Cytoskeletal Proteins/metabolism , Diabetes Mellitus/metabolism , Hyperglycemia/metabolism , NF-E2-Related Factor 2/metabolism , Reactive Oxygen Species/metabolism , Regeneration/physiology , Skin/metabolism , Wound Healing/physiology , Wounds and Injuries/metabolism , Adaptor Proteins, Signal Transducing/genetics , Animals , Blotting, Western , Cytoskeletal Proteins/genetics , Diabetes Mellitus/genetics , Fluorescent Antibody Technique , Glutathione , Hyperglycemia/genetics , Immunoprecipitation , Kelch-Like ECH-Associated Protein 1 , Mice , Mice, Inbred C57BL , Mice, Inbred Strains , NF-E2-Related Factor 2/genetics , NIH 3T3 Cells , Oxidative Stress/genetics , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction , Skin/injuries
7.
Ann Surg Oncol ; 23(2): 490-3, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26438436

ABSTRACT

BACKGROUND: Permanent paraffin subareolar biopsy during nipple-sparing mastectomy (NSM) tests for occult cancer at the nipple-areolar complex. Intraoperative subareolar frozen section can provide earlier detection intraoperatively. Cost analysis for intraoperative subareolar frozen section has never been performed. METHODS: NSM cases from 2006-2013 were reviewed. Patient records including financial charges were analyzed. RESULTS: Of 480 subareolar biopsies for NSM from 2006-2013, 21 were abnormal (4.4 %). A total of 307 of the subareolar biopsies included intraoperative frozen section. Of the 307, 12 (3.9 %) were abnormal with 7 of 12 detected on intraoperative frozen section. The median baseline charge for an intraoperative subareolar frozen section was $309 for an estimated total cost of $94,863 in 307 breasts. The median baseline charge for interval operative resection of a nipple-areolar complex following an abnormal subareolar pathology result was $11,021. Intraoperative subareolar biopsy avoided an estimated six return trips to the operating room for savings of $66,126. At our institution, routine use of intraoperative frozen section resulted in an additional $28,737 in healthcare charges or $95 per breast. CONCLUSIONS: We present the first cost analysis to evaluate intraoperative subareolar frozen section in NSM. This practice obviated an estimated six return trips to the operating room. With our institutional frequency of abnormal subareolar pathology, intraoperative frozen sections resulted in a marginal increased charge per mastectomy.


Subject(s)
Breast Neoplasms/economics , Costs and Cost Analysis , Intraoperative Care/economics , Mastectomy/economics , Nipples/pathology , Organ Sparing Treatments/economics , Biopsy, Needle , Breast Neoplasms/diagnosis , Breast Neoplasms/surgery , Female , Follow-Up Studies , Frozen Sections , Humans , Neoplasm Staging , Prognosis , Retrospective Studies
8.
Plast Reconstr Surg ; 135(5): 1342-1348, 2015 May.
Article in English | MEDLINE | ID: mdl-25919248

ABSTRACT

BACKGROUND: Otoplasty for prominent ears is a routine procedure that is generally met with satisfaction by patients and family members. A significant percentage of patients requesting otoplasty, however, have some degree of macrotia in addition to protruding ears. Combining ear reduction with traditional otoplasty allows correction of these deformities. There are few studies in the literature that describe ear reduction, and those that do, describe small subsets of patients. METHODS: A retrospective review was performed of the senior author's (C.H.T.) otoplasty procedures from 2010 to 2013. Charts were reviewed for patient demographics, preoperative assessment, surgical technique used, complications, and need for revision. All otoplasty procedures, primary or secondary, were included in the series. RESULTS: Over a 3-year period, 84 total otoplasty procedures were performed. Of these, 30 patients had some degree of scaphal reduction as a component of the procedure. Five patients (6 percent) also had shortening of the earlobes in addition to the scaphal reduction. Nineteen of the patients (23 percent) had an otoplasty previously (none performed by the senior author) but were not completely satisfied. Complications of reduction otoplasty were limited to a single patient with a suture protrusion behind the ear. None of the patients in this series have required reoperation. CONCLUSIONS: Scaphal reduction to modify the contour of the upper auricle and/or decrease the overall size of the ear can be a valuable adjunct to otoplasty and may be indicated in a larger than expected percentage of patients presenting for otoplasty. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.


Subject(s)
Ear Diseases/surgery , Ear, External/surgery , Otologic Surgical Procedures/methods , Patient Satisfaction , Plastic Surgery Procedures/methods , Suture Techniques , Adolescent , Adult , Child , Female , Follow-Up Studies , Humans , Male , Retrospective Studies , Treatment Outcome , Young Adult
9.
Plast Reconstr Surg ; 135(5): 838e-848e, 2015 May.
Article in English | MEDLINE | ID: mdl-25919266

ABSTRACT

BACKGROUND: Although the majority of nasal alterations in rhinoplasty result from either augmentation or reduction of bone and cartilaginous substructure, modifications of influential soft-tissue provide significant contribution to the final result. The depressor septi nasi muscle is a soft-tissue structure well known to influence the final result in rhinoplasty. The objective of this study was to perform a standardized, comprehensive review of relevant data published with regard to the depressor septi nasi muscle. METHODS: A comprehensive search of the terms "depressor septi muscle" and "depressor septi nasi muscle" was performed using the PubMed, MEDLINE, and Cochrane databases. Articles were reviewed for relevancy and included if criteria were met. A secondary review was performed of all articles cited, to maximize diligence. RESULTS: Forty-three articles were identified in the initial search. Thirteen of the 43 were found to meet inclusion criteria. Secondary search revealed additional studies meeting inclusion criteria. Altogether, there were 175 cadaver specimens and 821 surgically treated patients for which data were available. Anatomical reports and nomenclature were found to vary. Surgical approach and muscle treatment diverged, with objective data showing no superior method. CONCLUSIONS: Although variation exists in anatomical reports regarding the depressor septi nasi muscle, the prevailing thought is that it originates from the maxilla and/or orbicularis oris muscle. More importantly, the muscle inserts on the medial crura and adjacent soft tissue. Disruption of this relationship provides the basis for surgical treatment of tip descent on animation.


Subject(s)
Facial Muscles/surgery , Nasal Septum/surgery , Rhinoplasty/methods , Facial Expression , Humans
10.
Plast Reconstr Surg ; 135(5): 909e-918e, 2015 May.
Article in English | MEDLINE | ID: mdl-25919273

ABSTRACT

BACKGROUND: Facebook is the leading online media platform used by plastic surgeons. This study examined Facebook use among plastic surgeons and its perceived impact. METHODS: A survey on Facebook use was distributed to two groups of plastic surgeons: 500 with professional Facebook pages and 500 without Facebook pages. Responses were stripped of identifying information and analyzed for statistical significance (p < 0.05). RESULTS: One hundred twenty-three total surveys were completed (12.3 percent response rate). No respondents with Facebook reported a negative impact on their practice, whereas 57 percent reported a very positive or positive impact. There was no correlation with perceived impact and number of "likes." Perceived advantages of Facebook included facilitation of patient feedback/communication (77 percent) and increased practice exposure (67 percent). Many surgeons (15 to 36 percent) did not follow the direct impact of Facebook on their practices. Some reported that Facebook was responsible for only one to 50 professional Web site hits and less than 5 percent of their new patient referrals in the past year. Estimated conversion-to-surgery rates were highly variable for Facebook users and nonusers. Most Facebook nonusers (67 percent) expected a "neutral" impact, expressing more concerns about unsolicited advertising (51 percent) and wasting time (47 percent). CONCLUSIONS: Plastic surgeons tend to perceive Facebook's impact on their practices as positive, but most do not track its direct effects on professional Web site hits, new referrals, or conversion-to-surgery rates. Plastic surgeons using Facebook are encouraged to monitor these parameters to determine whether its continued use is actually worthwhile.


Subject(s)
Attitude , Referral and Consultation , Social Media/statistics & numerical data , Surgeons/psychology , Surgery, Plastic , Adult , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Retrospective Studies , Surveys and Questionnaires , Workforce
11.
Plast Reconstr Surg ; 135(5): 1295-1304, 2015 May.
Article in English | MEDLINE | ID: mdl-25835245

ABSTRACT

Three-dimensional surface imaging has gained clinical acceptance in plastic and reconstructive surgery. In contrast to computed tomography/magnetic resonance imaging, three-dimensional surface imaging relies on triangulation in stereophotography to measure surface x, y, and z coordinates. This study reviews the past, present, and future directions of three-dimensional topographic imaging in plastic surgery. Historically, three-dimensional imaging technology was first used in a clinical setting in 1944 to diagnose orthodontologic conditions. Karlan established its use in the field of plastic surgery in 1979, analyzing contours and documenting facial asymmetries. Present use of three-dimensional surface imaging has focused on standardizing patient topographic measurements to enhance preoperative planning and to improve postoperative outcomes. Various measurements (e.g., volume, surface area, vector distance, curvature) have been applied to breast, body, and facial topography to augment patient analysis. Despite the rapid progression of the clinical applications of three-dimensional imaging, current use of this technology is focused on the surgeon's perspective and secondarily the patient's perspective. Advancements in patient simulation may improve patient-physician communication, education, and satisfaction. However, a communal database of three-dimensional surface images integrated with emerging three-dimensional printing and portable information technology will validate measurements and strengthen preoperative planning and postoperative outcomes. Three-dimensional surface imaging is a useful adjunct to plastic and reconstructive surgery practices and standardizes measurements to create objectivity in a subjective field. Key improvements in three-dimensional imaging technology may significantly enhance the quality of plastic and reconstructive surgery in the near future.


Subject(s)
Imaging, Three-Dimensional/methods , Surgery, Computer-Assisted/methods , Surgery, Plastic/methods , Humans
13.
Ann Plast Surg ; 72(5): 515-20, 2014 May.
Article in English | MEDLINE | ID: mdl-24691319

ABSTRACT

Marjolin's ulcers are rare cutaneous malignancies that most commonly present as squamous cell carcinomas in previously injured, chronically inflamed, or scarred skin. Acute and chronic types have been distinguished by the length of latency; by definition, the acute type occurs within 12 months of injury whereas the chronic type appears over 12 months after injury. In this report, 3 cases of acute Marjolin's ulcers are described and questions are raised about the diagnosis of acute Marjolin's ulcer. Other than a discrepancy in lag time, it is unclear if there is any difference in clinical or histological characteristics or even prognosis between acute and chronic Marjolin's ulcers. In fact, the acute type may simply be a preemptive diagnosis that conveniently describes a carcinoma associated with a nonhealing wound and discovered within a short time span. Moreover, the rarity of the diagnosis and the relatively rapid rate of malignant degeneration from the inciting injury lead one to question whether the injury may have simply revealed or accelerated a previously existing occult cutaneous malignancy. With no definitive clinical, histological, or prognostic distinction between acute and chronic Marjolin's ulcers, the use of such terminology may not benefit a clinician's understanding or practice. In fact, it merely supports the clinical guideline that any nonhealing wound, acute or chronic, should be biopsied and sent for pathologic examination to ensure that it does not represent a Marjolin's ulcer.


Subject(s)
Carcinoma, Basal Cell/pathology , Neoplasms, Multiple Primary/pathology , Skin Neoplasms/pathology , Skin Ulcer/pathology , Adult , Biopsy , Burns/complications , Burns/surgery , Carcinoma, Basal Cell/etiology , Diagnosis, Differential , Fatal Outcome , Female , Hidradenitis Suppurativa/complications , Humans , Keratosis, Actinic/pathology , Male , Middle Aged , Prognosis , Skin Neoplasms/etiology , Skin Ulcer/etiology
14.
J Burn Care Res ; 35(1): 93-101, 2014.
Article in English | MEDLINE | ID: mdl-24390110

ABSTRACT

Burn contracture of the toes is a devastating sequela of thermal injury to the foot. Without proper treatment of toe burn contractures, patients suffer from significant functional and social limitations, including difficulties with activities of daily living. The authors classify the severity of toe burn scar contractures (TBSCs) by considering important characteristics of the deformity and tailor definitive surgical treatment based on the individual needs of the patient's condition. A retrospective review was performed on 20 patients who underwent a total of 32 reconstructive operations involving 275 TBSC procedures from 2000 to 2010. Multiple clinical, functional, and anatomic criteria were used to describe each patient's contracture as mild, moderate, or severe. Mild TBSC involved scarring of the superficial tissues only with no functional impairment; these were treated with scar release or local tissue rearrangement. Moderate TBSC involved soft tissue shortages requiring skin grafts and occasional closed joint capsulotomy. Severe TBSC caused the greatest impairment in function and involved burn injury to deeper structures. For these difficult contractures, a patient-specific technique was paramount to optimal reconstruction. There were six, three, and 11 patients with mild, moderate, and severe TBSC, respectively. The mean number of primary procedures per toe increased with increasing burn complexity from 1.1 procedures for mild, 1.5 for moderate, and 1.8 for severe groups, with severe TBSC undergoing more primary procedures overall (13.7 in severe vs 2.8 in mild TBSC). Complication rates per toe were highest for severe TBSC (59.0%). Only severe TBSC received secondary operations, and overall contracture recurrence was 35%. An individualized surgical approach based on TBSC severity is recommended for addressing burn contracture of the toes. Careful analysis of the clinical, functional, and anatomic characteristics of the burned foot determines the severity of each toe contracture and dictates the interventions necessary for reconstruction.


Subject(s)
Burns/surgery , Contracture/surgery , Dermatologic Surgical Procedures/methods , Toes/surgery , Adolescent , Burns/complications , Child , Contracture/etiology , Female , Humans , Male , Postoperative Complications , Recurrence , Reoperation/statistics & numerical data , Retrospective Studies , Skin Transplantation , Toes/injuries , Treatment Outcome
16.
Ann Plast Surg ; 70(2): 158-61, 2013 Feb.
Article in English | MEDLINE | ID: mdl-22214797

ABSTRACT

BACKGROUND: New insights into potential adverse effects of banked blood and improved infectious surveillance have led to questions regarding the utility of preoperative autologous blood donation. METHODS: A retrospective chart review of 153 patients undergoing abdominal free flap breast reconstruction was performed with the goal of determining the effect of an autologous blood donation program on clinical outcomes. Demographic and premorbid conditions were evaluated along with outcome variables including complication and transfusion rates. RESULTS: As expected, the autologous blood donor group (n = 96) was more likely to receive a blood transfusion of any kind compared with the nondonors (98% vs. 18%, P < 0.0001). Surprisingly, the mean number of allogeneic transfusions was not decreased (0.26 vs. 0.84, P = 0.066). The mean number of complications between groups were comparable (0.53 vs. 0.57, P = 0.687). CONCLUSION: We found neither significant benefit nor adverse effect from the practice of autologous blood banking for free flap breast reconstruction. The practice should be considered safe but not routinely recommended for free flap breast surgery.


Subject(s)
Blood Donors , Blood Transfusion, Autologous , Breast Neoplasms/surgery , Free Tissue Flaps , Mammaplasty/methods , Adult , Blood Transfusion, Autologous/adverse effects , Female , Humans , Middle Aged , Preoperative Period , Retrospective Studies , Treatment Outcome
17.
J Orthop Res ; 29(2): 204-10, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20806320

ABSTRACT

Local control of osteoblast differentiation and bone formation is not well understood. We have previously seen biphasic effects on cell differentiation in response to the short- and long-term exposure to IL-1ß in rat calvarial osteoblasts. To characterize the signaling pathway mechanisms regulating IL-1ß biphasic effects, we examined the contribution of mitogen-activated protein kinase (MAPK) family. Cells were pretreated with specific inhibitors to extracellular signal-regulated kinase (ERK, PD98059), p38 (SB203580), and c-JUN N-terminal kinase (JNK, SP600125), then co-cultured with IL-1ß for 2, 4, and 6 days. Cell differentiation was determined by measuring bone nodules after 10 days of culture. These inhibitors did not alter biphasic effects of IL-1ß on cell differentiation. However, PD98059 and U2016, another inhibitor of ERK activation robustly increased osteoblast differentiation compared to vehicle-treated control in a time- and dose-dependent manner. PD98059 appears to stimulate alkaline phosphatase (ALP) activity to promote cell differentiation, where IL-1ß appears to suppress it. Interestingly, continuous ERK inhibition with PD98059, after 2 and 4 days of IL-1ß treatment, enhanced the IL-1ß anabolic effect by increasing bone nodules formed. These observations provide a potential mechanism involving ERK pathway in osteoblasts differentiation and suggest that MAPK family may not directly regulate IL-1ß biphasic effects.


Subject(s)
Cell Differentiation , Interleukin-1beta/metabolism , MAP Kinase Signaling System , Mitogen-Activated Protein Kinases/metabolism , Osteoblasts/enzymology , Alkaline Phosphatase/metabolism , Animals , Animals, Newborn , Butadienes , Cells, Cultured , Cyclooxygenase 2/metabolism , Flavonoids , Mitogen-Activated Protein Kinases/antagonists & inhibitors , Nitric Oxide Synthase Type II/metabolism , Nitriles , Osteoblasts/cytology , Osteogenesis , Rats , Skull/cytology
18.
J Orthop Res ; 28(7): 958-64, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20108347

ABSTRACT

A rat calvarial cell model of osteoblast differentiation using the formation of bone nodules in vitro as an endpoint was used to assess the effects of IL-1beta on osteoblast differentiation. Short-term treatment (2 days) with IL-1beta early in culture resulted in increased nodule number and size as well as calcium content in contrast to long-term treatment (6 days) in cultures assessed at 10-12 days. This increase in bone formation was blocked by IL-1 receptor antagonists. Short-term treatment increased COX-2, prostaglandin (PGE(2)), and iNOS production. Exogenous PGE(2) with IL-1beta enhanced this effect. COX-2 inhibitors, indomethacin and N-39, blocked 50% of nodule formation. NO donor did not modify effects of IL-1beta, but iNOS inhibitor (1400W) partially blocked the effects. However, PGE(2) and NO donors could not rescue the decreased nodule number resulting from long-term IL-1beta treatment. The results of this study suggest a biphasic effect of IL-1beta on bone nodule formation activated by IL-1beta binding with IL-1 receptors, and the anabolic effect of early short-term treatment with IL-1beta is likely mediated by PGE without ruling out nitric oxide.


Subject(s)
Interleukin-1beta/metabolism , Osteoblasts/cytology , Osteoblasts/metabolism , Osteogenesis/physiology , Animals , Cell Differentiation/drug effects , Cell Differentiation/physiology , Cells, Cultured , Cyclooxygenase 2 Inhibitors/pharmacology , Dinoprostone/metabolism , Dinoprostone/pharmacology , Drug Synergism , Enzyme Activation/drug effects , Enzyme Activation/physiology , Indomethacin/pharmacology , Interleukin-1beta/pharmacology , Nitric Oxide Donors/pharmacology , Nitric Oxide Synthase Type II/metabolism , Osteoblasts/drug effects , Osteogenesis/drug effects , Rats , Receptors, Interleukin-1/metabolism , Skull/cytology
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