Re-Dosing del Nido cardioplegia in adult cardiac surgery: Perfusion characteristics and outcomes--Is there an optimal redosing strategy?

OBJECTIVES: del Nido cardioplegia is utilized for myocardial protection in adult patients undergoing cardiac surgery; however, no standardized re-dosing protocol exists. We describe perfusion characteristics and clinical outcomes in adult cardiac surgery patients who were re-dosed with del Nido cardioplegia. METHODS: Chart review was performed for adult patients undergoing cardiac surgery (specific inclusion/exclusion criteria below) who received exactly two doses of del Nido cardioplegia from 2012 to 2019; n = 542 patients. The main outcome was a composite endpoint comprised of operative mortality, myocardial infarction, post-operative cardiac support device (CSD), and postoperative decrease in ejection fraction (EF), which was analyzed via multivariable logistic regression (MVLR). A secondary analysis evaluated postoperative vasoactive-inotropic scores (VIS) via gamma log link regression (GLLR) as a more physiologic indication of myocardial recovery. RESULTS: MVLR demonstrated that increased total cardiopulmonary bypass (CPB) time was associated with a positive composite outcome (p < .001), whereas time between doses (p = .237) and the volume of each dose was not (p = .626). GLLR also demonstrated that prolonged CBP, decreased EF, congestive heart failure at time of surgery, and low hematocrit at the start of the surgery were all associated with higher VIS. CONCLUSIONS: In this retrospective study, variations in re-dosing strategy for del Nido cardioplegia do not affect postoperative outcomes and increased CPB time is associated with increased operative mortality, myocardial infarction, need for post-operative CSDs, and reduced postoperative EF, and increased VIS, irrespective of the re-dosing strategy. Further studies are warranted to to identify additional patient and operative characteristics that predispose to complications.

Increased hospital volume is associated with reduced mortality after thoracoabdominal aortic aneurysm repair.

OBJECTIVE: Contemporary data on outcomes in open thoracoabdominal aortic aneurysm (TAAA) repair are limited to reports from major aortic referral centers showing excellent outcomes. This study aimed to characterize the national experience of open TAAA repair using national outcomes data, with a primary focus on the association of hospital volume with mortality and morbidity. METHODS: The Nationwide Inpatient Sample was queried from 1998 to 2011, and all patients with a diagnosis of TAAA who underwent open operative repair were included. These patients were further stratified into tertiles based on the operative volume of the institution that performed the operation: low volume (LV), <3 cases/y; medium volume (MV), 3 to 11 cases/y; and high volume (HV), ≥12 cases/y. Baseline demographics as well as perioperative outcomes were compared between these groups. Multivariable logistic regression was performed to determine predictors of operative mortality and morbidity. Subgroup analyses were performed for patients presenting for elective surgery and for those presenting for urgent and emergent surgery. RESULTS: Overall operative mortality was 21% for the entire cohort. Operative mortality was higher at LV (26%) and MV (21%) centers compared with HV centers (15%; P < .001). This difference was similar in both elective surgery (LV, 18%; MV, 14%; HV, 12%; P < .001) and urgent and emergent surgery (LV, 34%; MV, 30%; HV, 19%; P < .001). Furthermore, rates of blood transfusion and acute renal failure were significantly lower in the HV group. Multivariable analysis revealed that compared with the HV group, patients operated on at LV centers (odds ratio [OR], 1.9, 95% confidence interval [CI], 1.7-2.1; P < .001) and MV centers (OR, 1.5; 95% CI, 1.4-1.7; P < .001) had at least 1.5 times the odds of in-hospital mortality. The HV group also had significantly lower odds of dying in the subgroup analyses of both elective surgery and urgent and emergent surgery. Increasing TAAA volume was associated with increased use of distal aortic perfusion (OR, 1.03; 95% CI, 1.02-1.03; P < .001). CONCLUSIONS: Patients with TAAA in the United States operated on at HV centers have significantly lower mortality and morbidity compared with patients operated on at lower volume centers. Consideration of referral to HV centers may be warranted, but further research is required to justify this conclusion.

Impact of Septal Myectomy Volume on Mitral-Valve Replacement Rate in Hypertrophic Cardiomyopathy Patients.

OBJECTIVE: Mitral regurgitation (MR) induced by systolic anterior motion in patients with hypertrophic cardiomyopathy (HCM) can frequently be abolished with a proficient septal myectomy (SM) without the need for mitral-valve replacement (MVR). ACC guidelines stress the importance of volume in improving outcomes after SM, but there is a lack of data measuring the impact of volume on the need for MVR during SM. This study was designed to assess the impact of institutional volume on MVR rates using national outcomes data. METHODS: The Nationwide Inpatient Sample was queried from 1998 to 2011 and a total of 6,207 patients had a diagnosis of HCM and a procedure code for SM. Outcomes were compared between patients who underwent SM (group I) and SM and MVR (group II). Furthermore, patients were stratified into 3 groups based on the number of SMs at the performing institution: low experience (1-24 cumulative SMs), medium experience (25-49 SMs), and high experience (>50 SMs). These patients underwent multivariable analysis to determine the impact of institutional volume on MVR rate. RESULTS: The total MVR rate was 26%. Perioperative outcomes were worse, i.e., there were higher rates of mortality, kidney injury, and urinary complications, in group II than in group I. Only 37.6% of patients were operated on at institutions meeting the guideline criteria of >50 cumulative SMs. When compared to patients in the high-experience group, patients in the low- (OR 2.7, 95% CI 2.3-3.2, p < 0.05) and medium-experience (OR 3.0, 95% CI 2.5-3.6, p < 0.05) groups were more likely to undergo MVR. CONCLUSION: Compared to reports from SM reference centers, national data suggest that MVR rates are quite high at SM. Patients undergoing SM at centers that do not meet the guideline standard have >2.5× the odds of undergoing MVR compared to those operated on at guideline-endorsed centers.

Outcomes of mechanical support for cardiogenic shock associated with late cardiac allograft failure.

BACKGROUND: Late graft failure (LGF) is an unresolved issue after orthotopic heart transplant (OHT). In this study, we report characteristics and outcomes of severe LGF requiring mechanical circulatory support (MCS). METHODS: All patients undergoing OHT from 2000 to 2018 at our center were reviewed. Patients re-admitted to the hospital for late graft failure (>3 months after initial discharge) and developing cardiogenic shock requiring MCS were identified. Outcomes and mortality were evaluated. RESULTS: Twenty-six patients were identified. Median age was 37.3 years (interquartile range: 28.2-47.6) and 69% were male. Median time from initial transplant to MCS was 2.9 years. Etiology of graft failure was rejection in 19 patients (73%), transplant coronary artery disease (tCAD) in 3 (12%), with mixed tCAD or rejection in 4 (15%).

Institutional Marfan syndrome surgical volume influences mitral valve surgical strategy in patients with Marfan syndrome.

BACKGROUND/AIM: The goal of this study was to evaluate trends in mitral valve (MV) operations performed on patients with Marfan syndrome (MfS) and determine the influence of an institution's MfS and MV surgical volume on MV surgical strategy in the US. METHODS: The Nationwide Inpatient Sample was queried from 1998 to 2011 and a total of 1126 patients with MfS were identified who underwent MV operations meeting our inclusion criteria. Linear regression was performed to assess trends of MV repair (MVr) rates over time. Patients were stratified into tertiles depending on the institution's annual MfS and MV surgical volumes. Multivariate analysis was used to determine the impact of institutional MV and MfS surgical volume on whether a patient received an MV replacement (MVR). RESULTS: The MVR rate was 60% for the entire cohort. There was a decreasing trend of MVR rates during the study period (82% in 1998-99 vs 49% in 2010-2011, P < .05). Multivariate analysis revealed that patients operated on at high (odds ratio [OR], 0.65; P < .05) and medium (OR, 0.66; P < .05) volume MfS centers were less likely to undergo MVR when compared to lower-volume MfS centers. In contrast, MV volume was not a significant predictor of surgical strategy in this cohort. CONCLUSION: The national MVR rate in the MfS population is higher than published reports. Data from this study suggest that MfS patients with indications for MV surgery should be referred to high-volume MfS surgical centers to have the best opportunity for MVr.

COR-KNOT-Induced Leaflet Perforation: How It Happens and How to Prevent It: A Case Report.

The COR-KNOT suture fastening device has dramatically improved the efficiency of valve suture fixation. Despite its relative ease of use, there are important considerations in deployment to limit the risk of prosthetic valve injury. Herein, we report a case of iatrogenic aortic bioprosthetic insufficiency caused by poorly positioned COR-KNOTs and outline technical strategies to ensure success.

Decreased serotonin transporter activity in the mitral valve contributes to progression of degenerative mitral regurgitation.

Degenerative mitral valve (MV) regurgitation (MR) is a highly prevalent heart disease that requires surgery in severe cases. Here, we show that a decrease in the activity of the serotonin transporter (SERT) accelerates MV remodeling and progression to MR. Through studies of a population of patients with MR, we show that selective serotonin reuptake inhibitor (SSRI) use and SERT promoter polymorphism 5-HTTLPR LL genotype were associated with MV surgery at younger age. Functional characterization of 122 human MV samples, in conjunction with in vivo studies in SERT-/- mice and wild-type mice treated with the SSRI fluoxetine, showed that diminished SERT activity in MV interstitial cells (MVICs) contributed to the pathophysiology of MR through enhanced serotonin receptor (HTR) signaling. SERT activity was decreased in LL MVICs partially because of diminished membrane localization of SERT. In mice, fluoxetine treatment or SERT knockdown resulted in thickened MV leaflets. Similarly, silencing of SERT in normal human MVICs led to up-regulation of transforming growth factor ß1 (TGFß1) and collagen (COL1A1) in the presence of serotonin. In addition, treatment of MVICs with fluoxetine not only directly inhibited SERT activity but also decreased SERT expression and increased HTR2B expression. Fluoxetine treatment and LL genotype were also associated with increased COL1A1 expression in the presence of serotonin in MVICs, and these effects were attenuated by HTR2B inhibition. These results suggest that assessment of both 5-HTTLPR genotype and SERT-inhibiting treatments may be useful tools to risk-stratify patients with MV disease to estimate the likelihood of rapid disease progression.

A novel dosing strategy of del Nido cardioplegia in aortic surgery.

Objective: While del Nido (DN) cardioplegia is increasingly used in cardiac surgery, knowledge is limited in its safety profile for operations with prolonged crossclamp time (CCT). We have introduced a unique redosing strategy for aortic surgery: all operations use DN with a 1000-mL initiation dose (750 mL antegrade, 250 mL retrograde) composed of 1:4 blood:DN crystalloid. At 90 minutes CCT and every 30 minutes thereafter, a 250-mL dose was introduced retrograde in a 4:1 ("reverse") ratio. Additionally, at 90 minutes CCT and every 90 minutes thereafter, a reverse ratio dose of approximately 100 to 400 mL was introduced via the right coronary artery. Here, we analyze the outcomes of our unique redosing strategy used. Methods: In total, 440 patients underwent aortic surgery between January 2015 and March 2021 under a single surgeon and received DN. Our primary end points were change in left ventricular ejection fraction (LVEF) and right ventricular systolic function based on echocardiography. Multivariable linear regression was used to analyze the relationship between CCT and outcomes. Results: The median was 61 years old (interquartile range, 51-69), and 23% were female. Indication was aneurysm in 65% and dissection in 24%. Median preoperative LVEF was 60% (55%-62%). Median CCT and cardiopulmonary bypass times were 135 minutes (93-165 minutes) and 181 minutes (142-218 minutes), respectively. In-hospital mortality occurred in 3%. Multivariable linear regression showed CCT was not associated with change in LVEF or change in right ventricular systolic function. Conclusions: Our unique method of redosing DN cardioplegia appears to provide safe and effective myocardial protection for aortic surgery.

Re-dosing of del Nido cardioplegia in adult cardiac surgery requiring prolonged aortic cross-clamp.

OBJECTIVES: Few data exist on the use of del Nido cardioplegia in adults, specifically during operations requiring prolonged aortic cross-clamp. In this pilot study, we evaluate outcomes of patients undergoing surgery with cross-clamp time >3 h based on re-dosing strategy, using either full dose (FD; 1:4 blood to crystalloid ratio) or dilute (4:1 blood to crystalloid ratio) solution. METHODS: Consecutive adult patients (>18 years) undergoing cardiac surgery from 2012 to 2018 with cross-clamp time >3 h were reviewed. Patients were excluded if del Nido cardioplegia was not used. Patients were categorized into FD or dilute groups based on re-dosing solution. Propensity score matching was used to control for baseline differences between groups. The primary endpoint was in-hospital mortality. Other outcomes examined included: postoperative mechanical support, arrhythmia, stroke, dialysis and cardiac function. RESULTS: Included for analysis were 173 patients (115 male) with median age of 63.8 (interquartile range 53.9-73.1). Major comorbidities included diabetes (45), cerebrovascular disease (34), hypertension (131), atrial fibrillation (52) and previous cardiac surgery (83). There were 108 patients (62%) who received FD re-dosing, while 65 (38%) received dilute. A greater proportion of patients in the dilute group received retrograde delivery, for both induction (32/108 vs 39/65, P < 0.001) and re-dose (50/108 vs 53/65, P < 0.001). After propensity score matching, in-hospital mortality was not different between groups (6/48 vs 1/48, P = 0.131). There were no differences in rates of postoperative mechanical circulatory support, stroke, left ventricular ejection fraction or right ventricle dysfunction. CONCLUSIONS: Del Nido cardioplegia has been used in complex cardiac surgery requiring prolonged cross-clamp. Re-dosing can be performed with either FD or dilute del Nido solution with no statistical difference in outcomes.

The role of sensory organs and the forebrain for the development of the craniofacial shape as revealed by Foxg1-cre-mediated microRNA loss.

Cranial development is critically influenced by the relative growth of distinct elements. Previous studies have shown that the transcription factor Foxg1 is essential the for development of the telencephalon, olfactory epithelium, parts of the eye and the ear. Here we investigate the effects of a Foxg1-cre-mediated conditional deletion of Dicer1 and microRNA (miRNA) depletion on mouse embryos. We report the rapid and complete loss of the telencephalon and cerebellum as well as the severe reduction in the ears and loss of the anterior half of the eyes. These losses result in unexpectedly limited malformations of anterodorsal aspects of the skull. We investigated the progressive disappearance of these initially developing structures and found a specific miRNA of nervous tissue, miR-124, to disappear before reduction in growth of the specific neurosensory areas. Correlated with the absence of miR-124, these areas showed numerous apoptotic cells that stained positive for anticleaved caspase 3 and the phosphatidylserine stain PSVue® before the near or complete loss of those brain and sensory areas (forebrain, cerebellum, anterior retina, and ear). We conclude that Foxg1-cre-mediated conditional deletion of Dicer1 leads to the absence of functional miRNA followed by complete or nearly complete loss of neurons. Embryonic neurosensory development therefore depends critically on miRNA. Our data further suggest that loss of a given neuronal compartment can be triggered using early deletion of Dicer1 and thus provides a novel means to genetically remove specific neurosensory areas to investigate loss of their function on morphology (this study) or signal processing within the brain.

Higher Institutional Volume Reduces Mortality in Reoperative Proximal Thoracic Aortic Surgery.

OBJECTIVE: This study aims to determine the impact of institutional volume on mortality in reoperative proximal thoracic aortic surgery patients using national outcomes data. METHODS: The Nationwide Inpatient Sample was queried from 1998 to 2011 for patients with diagnoses of thoracic aneurysm and/or dissection who underwent open mediastinal repair. A total of 103,860 patients were identified. A total of 1,430 patients had prior cardiac surgery. Patients were further stratified into groups by institutional aortic volume: low (<12 cases/year), medium (12-39 cases/year), and high (40+ cases/year) volume. Multivariable risk-adjusted analysis accounting for emergent status and aortic dissection among other factors was performed to determine the impact of institutional volume on mortality. RESULTS: Overall mortality was 12% in the reoperative population. When the redo cohort was divided into tertiles, high-volume group had a 5% operative mortality compared with 9 and 15% for the medium- and low-volume groups, respectively. Multivariable analysis revealed that patients operated on at low- (odds ratio [OR] = 5.0, 95% confidence interval [CI]: 2.6-9.6, p < 0.001) and medium-volume centers (OR = 2.1, 95% CI: 1.1-4.2, p = 0.03) had higher odds of mortality when compared with patients operated on at high-volume centers. CONCLUSIONS: High-volume aortic centers can significantly reduce mortality for reoperative aortic surgery, compared with lower volume institutions.

The Rapid Transformation of Cardiac Surgery Practice in the Coronavirus Disease 2019 (COVID-19) Pandemic: Insights and Clinical Strategies From a Center at the Epicenter.

BACKGROUND: The onset of the coronavirus disease 2019 (COVID-19) pandemic has forced our cardiac surgery program and hospital to enact drastic measures that has forced us to change how we care for cardiac surgery patients, assist with COVID-19 care, and enable support for the hospital in terms of physical resources, providers, and resident training. METHODS: In this review, we review the cardiovascular manifestations of COVID-19 and describe our system-wide adaptations to the pandemic, including the use of telemedicine, how a severe reduction in operative volume affected our program, the process of redeployment of staff, repurposing of residents into specific task teams, the creation of operation room intensive care units, and the challenges that we faced in this process. RESULTS: We offer a revised set of definitions of surgical priority during this pandemic and how this was applied to our system, followed by specific considerations in coronary/valve, aortic, heart failure and transplant surgery. Finally, we outline a path forward for cardiac surgery for the near future. CONCLUSIONS: We recognize that individual programs around the world will eventually face COVID-19 with varying levels of infection burden and different resources, and we hope this document can assist programs to plan for the future.

The rapid transformation of cardiac surgery practice in the coronavirus disease 2019 (COVID-19) pandemic: insights and clinical strategies from a centre at the epicentre.

OBJECTIVES: The onset of the coronavirus disease 2019 (COVID-19) pandemic has forced our cardiac surgery programme and hospital to enact drastic measures that has forced us to change how we care for cardiac surgery patients, assist with COVID-19 care and enable support for the hospital in terms of physical resources, providers and resident training. METHODS: In this review, we review the cardiovascular manifestations of COVID-19 and describe our system-wide adaptations to the pandemic, including the use of telemedicine, how a severe reduction in operative volume affected our programme, the process of redeployment of staff, repurposing of residents into specific task teams, the creation of operation room intensive care units, and the challenges that we faced in this process. RESULTS: We offer a revised set of definitions of surgical priority during this pandemic and how this was applied to our system, followed by specific considerations in coronary/valve, aortic, heart failure and transplant surgery. Finally, we outline a path forward for cardiac surgery for the near future. CONCLUSIONS: We recognize that individual programmes around the world will eventually face COVID-19 with varying levels of infection burden and different resources, and we hope this document can assist programmes to plan for the future.

The rapid transformation of cardiac surgery practice in the coronavirus disease 2019 (COVID-19) pandemic: Insights and clinical strategies from a center at the epicenter.

BACKGROUND: The onset of the coronavirus disease 2019 (COVID-19) pandemic has forced our cardiac surgery program and hospital to enact drastic measures that has forced us to change how we care for cardiac surgery patients, assist with COVID-19 care, and enable support for the hospital in terms of physical resources, providers, and resident training. METHODS: In this review, we review the cardiovascular manifestations of COVID-19 and describe our system-wide adaptations to the pandemic, including the use of telemedicine, how a severe reduction in operative volume affected our program, the process of redeployment of staff, repurposing of residents into specific task teams, the creation of operation room intensive care units, and the challenges that we faced in this process. RESULTS: We offer a revised set of definitions of surgical priority during this pandemic and how this was applied to our system, followed by specific considerations in coronary/valve, aortic, heart failure and transplant surgery. Finally, we outline a path forward for cardiac surgery for the near future. CONCLUSIONS: We recognize that individual programs around the world will eventually face COVID-19 with varying levels of infection burden and different resources, and we hope this document can assist programs to plan for the future.

Improving Outcomes of Iatrogenic Type A Aortic Dissection during Cardiac Surgery.

BACKGROUND: Iatrogenic Type A aortic dissection (IAD) is a rare but devastating complication of cardiac and aortic surgery with reported operative mortality of 30 to 50%. In this study, we report our experience with IAD and propose a standardized approach to management. METHODS: From January 1, 2000 through December 31, 2016, 23,275 patients underwent cardiac surgery at our institution. We identified 15 patients who developed IAD. Our approach to management included (1) immediate repair, (2) involvement of a second attending surgeon, (3) aggressive monitoring of malperfusion, (4) securing true lumen arterial perfusion access and systemic cooling, and (5) performance of hemiarch or total arch replacement based on the presence of suspected brain malperfusion. The index operation was also completed at the same time. Patient preoperative characteristics, operative sequence and technique, complications, and outcomes were analyzed with chart review. RESULTS: The incidence of IAD at our institution was 0.06% (n = 15). A disproportionate percentage of patients had aneurysmal ascending aortas (33.3%). The index surgery consisted of aortic surgery in five patients (33.3%), coronary bypass in three patients, valve surgery in five patients, and transplantation in one patient. The mechanism of dissection was aortic cannulation in 66.7% and aortic root vent site cannulation in 13.3%. In 46.7% of patients, the IAD was first recognized based on clinical evidence such as aortic hematoma, pericardial bleeding, or abnormal perfusion line pressures. In 40.0%, the diagnosis was made with intraoperative echocardiography without any clinical manifestations. The timing of the diagnosis was at the initiation of cardiopulmonary bypass initiation in 60.0%, while in 40.0% it was recognized after discontinuation of bypass. Hemiarch was done in 73.3% and total arch replacement performed in 13.3%. Isolated ascending repairs were done in two patients. Bypass and cross-clamp times were 229.5 ± 212.7 minutes and 130.5 ± 109.5 minutes, respectively. In-hospital mortality in our cohort was 6.7%. While stroke occurred in one patient, no visceral organ malperfusion was recognized. CONCLUSIONS: Incidence of IAD is low with cannulation of an aneurysmal aorta being a risk factor. A standardized approach may result in reduced operative mortality.

Atrial arrhythmias after lung transplantation: Incidence and risk factors in 652 lung transplant recipients.

OBJECTIVES: Atrial arrhythmia (AA) after lung transplantation (LTx) is a potentially morbid event often associated with increased length of hospital stay. Predictors of postsurgical AA, however, are incompletely understood. We characterized the incidence and predisposing risk factors for AA in patients undergoing LTx. METHODS: A retrospective analysis of prospectively collected data was conducted to identify LTx recipients between January 2008 and October 2013. Patients were divided into 2 groups on the basis of postoperative AA development. Univariable and multivariable analyses were performed to define differences between groups and identify factors associated with AA. Survival differences were assessed by the use of competing risks methodology. RESULTS: A total of 198 of 652 (30.4%) patients developed AA at a median onset of 5 days after transplant. Increasing age (hazard ratio [HR] 1.03 per additional year, P < .001) and previous coronary artery bypass grafting (HR 2.77, P = .002) were found to be independent risk factors. Counterintuitively, patients with a medical history of AA before LTx had a lower incidence of postoperative AA. Preoperative beta-blocker usage was not a significant predictor of postoperative AA. Postoperative AA was a significant predictor of long-term mortality (HR 1.63, P = .007) when we adjusted for other risk factors. CONCLUSIONS: AA is a common occurrence after LTx, occurring with greatest frequency in the first postoperative week, and results in a significant reduction in long-term survival. Increasing age and before coronary artery bypass grafting were identified as independent risk factors for AA development. Better understanding of these risk factors may improve identification of patients at heightened risk after transplantation.

Inhibition of CK2 binding to BMPRIa induces C2C12 differentiation into osteoblasts and adipocytes.

BMP2 is a growth factor that regulates the cell fate of mesenchymal stem cells into osteoblast and adipocytes. However, the detailed signaling pathways and mechanism are unknown. We previously reported a new interaction of Casein kinase II (CK2) with the BMP receptor type-Ia (BMPRIa) and demonstrated using mimetic peptides CK2.1, CK2.2 and CK2.3 that the release of CK2 from BMPRIa activates Smad signaling and osteogenesis. Previously, we showed that mutation of these CK2 sites on BMPRIa (MCK2.1 (476S-A), MCK2.2 (324S-A) and MCK2.3 (214S-A)) induced osteogenesis. However, one mutant MCK2.1 induced osteogenesis similar to overexpression of wild type BMPRIa, suggesting that the effect of this mutant on mineralization was due to overexpression. In this paper we investigated the signaling pathways involved in the CK2-BMPRIa mediated osteogenesis and identified a new signaling pathway activating adipogenesis dependent on the BMPRIa and CK2 association. Further the mechanism for adipogenesis and osteogenesis is specific to the CK2 interaction site on BMPRIa. In detail our data show that overexpression of MCK2.2 induced osteogenesis was dependent on Caveolin-1 (Cav1) and the activation of the Smad and mTor pathways, while overexpression of MCK2.3 induced osteogenesis was independent of Caveolin-1 without activation of Smad pathway. However, MCK2.3 induced osteogenesis via the MEK pathway. The adipogenesis induced by the overexpression of MCK2.2 in C2C12 cells was dependent on the p38 and ERK pathways as well as Caveolin-1. These data suggest that signaling through BMPRIa used two different signaling pathways to induce osteogenesis dependent on CK2. Additionally the data supports a signaling pathway initiated in caveolae and one outside of caveolae to induce mineralization. Moreover, they reveal the signaling pathway of BMPRIa mediated adipogenesis.