Browsing by Author "Kacena, Melissa A."
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Item Aging negatively impacts the ability of megakaryocytes to stimulate osteoblast proliferation and bone mass(Elsevier, 2019) Maupin, Kevin A.; Himes, Evan R.; Plett, Artur P.; Chua, Hui Lin; Singh, Pratibha; Ghosh, Joydeep; Mohamad, Safa F.; Abeysekera, Irushi; Fisher, Alexa; Sampson, Carol; Hong, Jung-Min; Childress, Paul; Alvarez, Marta; Srour, Edward F.; Bruzzaniti, Angela; Pelus, Louis M.; Orschell, Christie M.; Kacena, Melissa A.; Orthopaedic Surgery, School of MedicineOsteoblast number and activity decreases with aging, contributing to the age-associated decline of bone mass, but the mechanisms underlying changes in osteoblast activity are not well understood. Here, we show that the age-associated bone loss critically depends on impairment of the ability of megakaryocytes (MKs) to support osteoblast proliferation. Co-culture of osteoblast precursors with young MKs is known to increase osteoblast proliferation and bone formation. However, co-culture of osteoblast precursors with aged MKs resulted in significantly fewer osteoblasts compared to co-culture with young MKs, and this was associated with the downregulation of transforming growth factor beta. In addition, the ability of MKs to increase bone mass was attenuated during aging as transplantation of GATA1low/low hematopoietic donor cells (which have elevated MKs/MK precursors) from young mice resulted in an increase in bone mass of recipient mice compared to transplantation of young wild-type donor cells, whereas transplantation of GATA1low/low donor cells from old mice failed to enhance bone mass in recipient mice compared to transplantation of old wild-type donor cells. These findings suggest that the preservation or restoration of the MK-mediated induction of osteoblast proliferation during aging may hold the potential to prevent age-associated bone loss and resulting fractures.Item Alterations to maternal cortical and trabecular bone in multiparous middle-aged mice(Hylonome, 2017-11) Gu, Alex; Sellamuthu, Rajendran; Himes, Evan; Childress, Paul J.; Pelus, Louis M.; Orschell, Christie M.; Kacena, Melissa A.; Orthopaedic Surgery, School of MedicineObjectives: During the reproductive cycle, altered calcium homeostasis is observed due to variable demand for mineral requirements. This results in increased bone resorption during the time period leading up to parturition and subsequent lactation. During lactation, women will lose 1-3% of bone mineral density per month, which is comparable to the loss experienced on an annual basis post-menopausal. The purpose of this study was to determine the effect of parity on bone formation in middle-aged mice. Methods: Mice were mated and grouped by number of parity and compared with age matched nulliparous controls. Measurements were taken of femoral trabecular and cortical bone. Calcium, protein and alkaline phosphatase levels were also measured. Results: An increase in trabecular bone mineral density was observed when comparing mice that had undergone parity once to the nulliparous control. An overall decrease in trabecular bone mineral density was observed as parity increased from 1 to 5 pregnancies. No alteration was seen in cortical bone formation. No difference was observed when calcium, protein and alkaline phosphatase levels were assessed. Conclusions: This study demonstrates that number of parity has an impact on trabecular bone formation in middle-aged mice, with substantial changes in bone density seen among the parous groups.Item Alterations to maternal cortical and trabecular bone in multiparous middle-aged mice(Hylonome, 2017-12-01) Gu, A.; Sellamuthu, R.; Himes, E.; Childress, P.J.; Pelus, L.M.; Orschell, C.M.; Kacena, Melissa A.; Orthopaedic Surgery, School of MedicineOBJECTIVES: During the reproductive cycle, altered calcium homeostasis is observed due to variable demand for mineral requirements. This results in increased bone resorption during the time period leading up to parturition and subsequent lactation. During lactation, women will lose 1-3% of bone mineral density per month, which is comparable to the loss experienced on an annual basis post-menopausal. The purpose of this study was to determine the effect of parity on bone formation in middle-aged mice. METHODS: Mice were mated and grouped by number of parity and compared with age matched nulliparous controls. Measurements were taken of femoral trabecular and cortical bone. Calcium, protein and alkaline phosphatase levels were also measured. RESULTS: An increase in trabecular bone mineral density was observed when comparing mice that had undergone parity once to the nulliparous control. An overall decrease in trabecular bone mineral density was observed as parity increased from 1 to 5 pregnancies. No alteration was seen in cortical bone formation. No difference was observed when calcium, protein and alkaline phosphatase levels were assessed. CONCLUSIONS: This study demonstrates that number of parity has an impact on trabecular bone formation in middle-aged mice, with substantial changes in bone density seen among the parous groups.Item Analysis of the effects of spaceflight and local administration of thrombopoietin to a femoral defect injury on distal skeletal sites(Springer Nature, 2021-03-26) Zamarioli, Ariane; Campbell, Zachery R.; Maupin, Kevin A.; Childress, Paul J.; Ximenez, Joao P.B.; Adam, Gremah; Chakraborty, Nabarun; Gautam, Aarti; Hammamieh, Rasha; Kacena, Melissa A.; Orthopaedic Surgery, School of MedicineWith increased human presence in space, bone loss and fractures will occur. Thrombopoietin (TPO) is a recently patented bone healing agent. Here, we investigated the systemic effects of TPO on mice subjected to spaceflight and sustaining a bone fracture. Forty, 9-week-old, male, C57BL/6 J were divided into 4 groups: (1) Saline+Earth; (2) TPO + Earth; (3) Saline+Flight; and (4) TPO + Flight (n = 10/group). Saline- and TPO-treated mice underwent a femoral defect surgery, and 20 mice were housed in space ("Flight") and 20 mice on Earth for approximately 4 weeks. With the exception of the calvarium and incisor, positive changes were observed in TPO-treated, spaceflight bones, suggesting TPO may improve osteogenesis in the absence of mechanical loading. Thus, TPO, may serve as a new bone healing agent, and may also improve some skeletal properties of astronauts, which might be extrapolated for patients on Earth with restraint mobilization and/or are incapable of bearing weight on their bones.Item Association of Urinary and Blood Concentrations of Heavy Metals with Measures of Bone Mineral Density Loss: a Data Mining Approach with the Results from the National Health and Nutrition Examination Survey(Springer, 2021) Ximenez, João Paulo B.; Zamarioli, Ariane; Kacena, Melissa A.; Barbosa, Rommel Melgaço; Barbosa, Fernando, Jr.; Orthopaedic Surgery, School of MedicineOsteoporosis and its consequence of fragility fracture represent a major public health problem. Human exposure to heavy metals has received considerable attention over the last decades. However, little is known about the influence of co-exposure to multiple heavy metals on bone density. The present study aimed to examine the association between exposure to metals and bone mineral density (BMD) loss. Blood and urine concentrations of 20 chemical elements were selected from 3 cycles (2005–2010) NHANES (National Health and Nutrition Examination Survey), in which we included white women over 50 years of age and previously selected for BMD testing (N = 1892). The bone loss group was defined as participants having T-score < − 1.0, and the normal group was defined as participants having T-score ≥ − 1.0. We developed classification models based on support vector machines capable of determining which factors could best predict BMD loss. The model which included the five-best features-selected from the random forest were age, body mass index, urinary concentration of arsenic (As), cadmium (Cd), and tungsten (W), which have achieved high scores for accuracy (92.18%), sensitivity (90.50%), and specificity (93.35%). These data demonstrate the importance of these factors and metals to the classification since they alone were capable of generating a classification model with a high prediction of accuracy without requiring the other variables. In summary, our findings provide insight into the important, yet overlooked impact that arsenic, cadmium, and tungsten have on overall bone health.Item Authorship Trends in the Journal of Orthopaedic Research: A Bibliometric Analysis(Wiley, 2018) Seetharam, Abhijit; Ali, Mohammed T.; Wang, Christine Y.; Schultz, Katherine E.; Fischer, James P.; Lunsford, Shatoria; Whipple, Elizabeth C.; Loder, Randall T.; Kacena, Melissa A.; Orthopaedic Surgery, School of MedicinePublications are an important tool to measure one's success and achievement in academia. They can help propel a career forward and move one into a position of leadership. The overall purpose of this study was to investigate changes in bibliometric variables, authorship, and collaboration trends in the Journal of Orthopaedic Research (JOR®), since its inception in 1983. A bibliometric analysis was completed for all manuscripts meeting the inclusion criteria (638), which were published throughout the inaugural year plus one representative year of each decade. Several parameters were investigated including numbers of manuscripts, authors, collaborating institutions/countries, references, pages, and citations; region of origin and gender of authors over time and by region were main focuses. Significant increases over time were observed in all bibliometric variables analyzed except in the number of pages and citations. There was an approximate 27 percentage point increase for both female first and corresponding authors from 1983 to 2015. While this is most likely due to the increase in the number of women that have entered the field over time, similar increases in the percentage of women holding positions on the JOR editorial board or in leadership positions within in the field may have also contributed to improvements in gender parity. Understanding changes in publishing characteristics over time, by region, and by gender are critical, especially with the rising demands of publishing in academia. JOR has seen increase in most variables analyzed, including improvements in authorship by women in the field of orthopaedic research.Item Authorship Trends Over the Past 30-Years in the Annals of Biomedical Engineering(Springer, 2019-05) Aguilar, Izath Nizeet; Ganesh, Venkateswaran; Mannfeld, Rachel; Gorden, Riley; Hatch, Jennifer M.; Lunsford, Shatoria; Whipple, Elizabeth C.; Loder, Randall T.; Kacena, Melissa A.; Orthopaedic Surgery, School of MedicineIn academia, manuscripts serve as an important component of career development. The past several years have seen heightened evaluation of the role of the gender gap in career advancement, as well as other bibliometric changes in publications. We therefore analyzed authorship and publication trends in the Annals of Biomedical Engineering over the past three decades (one complete year of manuscripts for each decade; 1986, 1996, 2006, and 2016). The variables analyzed were number of authors per manuscript, numerical position of the corresponding author, number of collaborating institutions and countries, number of references, and number of citations per manuscript. The gender of both the first and corresponding authors was identified and analyzed over time and by region. Globally, the percentage of female first and corresponding authors significantly increased from 0% in 1986 to 28.6% (p = 0.003) and 20.4% (p = 0.0009), respectively, in 2016. Although there were significant differences regarding female first and corresponding author over time, they did not vary by region of origin (p = 0.5 and 0.2, respectively). Overall, these findings highlight the improvements made and the challenges that still exist related to publishing within the bioengineering field.Item Benchside to Bedside: The Launching of a Novel Bone Healing Agent(Office of the Vice Chancellor for Research, 2013-04-05) Bemenderfer, Thomas; Busenbark, John; Kansal, Jagan; Chu, Tien-Min Gabriel; Kacena, Melissa A.The ability to evolve a nascent idea into a successful entity requires navigation through a number of perils known to debilitate new ventures. Embryonic firms (or ideas) require sufficient development; from establishing an unambiguous approach, to attaining the necessary capital for evolution and growth, to fostering an environment and market for the idea or product. In the venture community, there are a number of advocates who possess the ability to contribute to new ventures (e.g. venture community support functions, venture capitalists, or informal contributors), and these individuals help navigate the startup or idea through inception to effectuation. Academic faculty, though, who often are not engrained into the local venture community, are frequently disadvantaged because their ideas or new firms come as an ancillary to their primary work. Already potentially impeded by the challenges presented by the legal constraints of providing sufficient equity for ideas to the university, developing a clear, effective path to market can be difficult for academic faculty. In addition to the systemic uncertainty, difficulty, and impediments faced by all entrepreneurs, academic faculty are constrained by limited time, funding, experience, and other resources – all related to their inclusion in the university or system. In order to alleviate these constraints and propel cutting-edge scientific breakthroughs and technological development, Innovation-to-Enterprise Central (ITEC) was initiated to assist academic faculties’ developments into the market – where, ultimately, these products will have the greatest utility to society. Osetofuse is an embryonic firm in the nascent stages of conceptualizing a revolutionary new product, which uses thrombopoietin as a novel bone healing agent. Through the ITEC program, Osteofuse has been able to facilitate the exploration of the potential value (clinically, economically, and societally) of its research and how the initial idea can be developed into a commercialized and monetized product. In the process, it has developed mechanisms to gauge the market’s acceptance of the product, the intellectual property and legal issue constraints facing the idea, potential commercialization streams and related valuations for marketization, and a quantitative analysis of projected revenue provisions. ITEC fosters continual compounding of knowledge capacity, as the trajectory of Osteofuse has not only inclined, but redirected because of specific uncovered data and insight from the program. As a result, Osteofuse has undergone dramatic transformation; in terms of both its formal identity and the potential approach to the market.Item Bibliometric analysis of authorship trends and collaboration dynamics over the past three decades of BONE's publication history(Elsevier, 2018-02) Khan, Faisal; Sandelski, Morgan M.; Rytlewski, Jeff; Lamb, Jennifer; Pedro, Christina; Adjei, Michael B. N.; Lunsford, Shatoria; Fischer, James P.; Wininger, Austin E.; Whipple, Elizabeth C.; Loder, Randall T.; Kacena, Melissa A.; Orthopaedic Surgery, School of MedicineThe existence of a gender gap in academia has been a hotly debated topic over the past several decades. It has been argued that due to the gender gap, it is more difficult for women to obtain higher positions. Manuscripts serve as an important measurement of one's accomplishments within a particular field of academia. Here, we analyzed, over the past 3 decades, authorship and other trends in manuscripts published in BONE, one of the premier journals in the field of bone and mineral metabolism. For this study, one complete year of manuscripts was evaluated (e.g. 1985, 1995, 2005, 2015) for each decade. A bibliometric analysis was then performed of authorship trends for those manuscripts. Analyzed fields included: average number of authors per manuscript, numerical position of the corresponding author, number of institutions collaborating on each manuscript, number of countries involved with each manuscript, number of references, and number of citations per manuscript. Each of these fields increased significantly over the 30-year time frame (p < 10− 6). The gender of both the first and corresponding authors was identified and analyzed over time and by region. There was a significant increase in the percentage of female first authors from 23.4% in 1985 to 47.8% in 2015 (p = 0.001). The percentage of female corresponding authors also increased from 21.2% in 1985 to 35.4% in 2015 although it was not significant (p = 0.07). With such a substantial emphasis being placed on publishing in academic medicine, it is crucial to comprehend the changes in publishing characteristics over time and geographical region. These findings highlight authorship trends in BONE over time as well as by region. Importantly, these findings also highlight where challenges still exist.Item Bibliometric Analysis of Female Authorship Trends and Collaboration Dynamics Over JBMR's 30-Year History(Wiley, 2017) Wininger, Austin E.; Fischer, James P.; Likine, Elive F.; Gudeman, Andrew S.; Brinker, Alexander R.; Ryu, Jonathan; Maupin, Kevin A.; Lunsford, Shatoria; Whipple, Elizabeth C.; Loder, Randall T.; Kacena, Melissa A.; Department of Orthopaedic Surgery, School of MedicineIn academia, authorship is considered a currency and is important for career advancement. As the Journal of Bone and Mineral Research (JBMR) is the highest-ranked journal in the field of bone, muscle, and mineral metabolism and is the official publication of the American Society for Bone and Mineral Research, we sought to examine authorship changes over JBMR's 30-year history. Two bibliometric methods were used to collect the data. The “decade method” included all published manuscripts throughout 1 year in each decade over the past 30 years starting with the inaugural year, yielding 746 manuscripts for analysis. The “random method” examined 10% of published manuscripts from each of the 30 years, yielding 652 manuscripts for analysis. Using both methods, the average number of authors per manuscript, numerical location of the corresponding author, number of collaborating institutions, number of collaborating countries, number of printed manuscript pages, and the number of times each manuscript was cited all significantly increased between 1986 and 2015 (p < 10−4). Using the decade method, there was a significant increase in the percentage of female first authors over time from 35.8% in 1986 to 47.7% in 2015 (p = 0.02), and this trend was confirmed using the random method. The highest percentage of female first authors in 2015 was in Europe (60.0%), and Europe also had the most dramatic increase in female first authors over time (more than double in 2015 compared with 1986). Likewise, the overall number of female corresponding authors significantly increased during the past 30 years. With the increasing demands of publishing in academic medicine, understanding changes in publishing characteristics over time and by geographical region is important. These findings highlight JBMR's authorship trends over the past 30 years and demonstrate those countries having the most changes and where challenges still exist.