ERK5 negatively regulates Kruppel-like factor 4 and promotes osteogenic lineage cell proliferation in response to MEK5 overexpression or fluid shear stress.

Aim of the study: Fluid shear stress (FSS) plays a critical role in osteoblast proliferation via extracellular signal-regulated kinase 5 (ERK5). Kruppel-like factor 4 (KLF4) knockout robustly enhances bone formation due to increased osteoblast differentiation and mineralization. However, the effect of KLF4 on osteoblast proliferation is unresolved. Therefore, the aim of our study was to investigate the effect of KLF4 on osteogenic lineage cell proliferation and the relationship between KLF4 and ERK5. Materials and methods: MC3T3-E1 cells were treated with FSS and/or KLF4 siRNA, cell viability was accessed by Edu labeling and CCK-8 assay, and proliferative gene expression were assessed by PCR array. Bone marrow stromal cells (BMSCs) were infected with adenovirus expressing KLF4 and/or constitutively active MEK5, cell viability was evaluated using crystal violet staining, colony formation assay, and cell WST1 assay. The levels of KLF4 and ERK5 phosphorylation were identified through qRT-PCR and western blot, respectively. Results: KLF4 expression was significantly down-regulated by FSS exposure, however, this was reversed by ERK5 siRNA. KLF4 overexpression inhibited colony formation efficiency and cell viability in BMSCs. Adenoviruses expressing constitutively active MEK5 increased ERK5 phosphorylation, which inhibited KLF4 expression, and promoted BMSC proliferation. FSS-induced osteoblast proliferation also involved elevation of Cyclin B2 and Cdc14b as well as repressed expression of P27. Conclusions: KLF4 negatively regulates osteogenic lineage cell proliferation, and ERK5 negatively regulates KLF4 expression and promotes osteogenic lineage cell proliferation.

Second Toe-to-thumb Transfer Using Intramedullary Screw Fixation after Traumatic Thumb Amputation.

Loss of the thumb secondary to trauma leads to significant disability due to the digit contributing 40% of overall hand function. Toe-to-thumb transfer has been a well-studied reconstructive method as a means to restore function after thumb amputation. First described in 1969 by Cobbett and colleagues, toe-to-thumb transfers have undergone several modifications in technique to better improve functional and aesthetic outcomes, including toe wrap-around flaps, trimmed great toe transfer, and second toe transfers. Although these methods have allowed patients to retain use of the thumb, traditional interosseous wire reattachment often leads to significant stiffness and need for prolonged rehabilitation to regain maximal function. Intramedullary screw fixation has been increasingly used in phalanx and metacarpal fractures, but its implementation outside of these contexts is not well reported. Here, we present a case of a patient who presented with traumatic thumb amputation and was treated with second toe-to-thumb transfer with intramedullary screw fixation, a novel mode of interosseous rigid fixation in toe-to-hand surgery. Postoperatively, our patient was able to begin mobilizing the new thumb immediately, which allowed for earlier return to work. We believe our technique can be applied to other cases of second toe, as well as great toe, transfers to improve length of recovery and rehabilitation postoperatively.

Health Disparities in Patients Seeking Physiological Surgical Treatment for Lymphedema.

BACKGROUND: Previous studies have demonstrated racial disparities in breast cancer treatment and secondary lymphedema. However, no studies have yet examined the effects of race and socioeconomic status on physiological surgical treatment for lymphedema. The authors aimed to evaluate whether disparities exist within patients seeking physiological surgical lymphedema treatment. METHODS: A retrospective review was performed of patients presenting for physiological surgical treatment of lymphedema from 2013 to 2019. Data on demographics, medical history, socioeconomic factors, lymphedema, and treatments were collected. RESULTS: A total of 789 patients (712 women and 77 men) seeking physiological surgical treatment of lymphedema were selected. Their mean age was 54.4 ± 13.4 years. A total of 620 patients (78.5%) self-reported as White, 120 (15.2%) as Black, 17 (2.2%) as Asian, five (0.6%) as Hispanic, and eight (2.4%) as multiracial. A total of 566 patients (71.7%) met criteria for surgical candidacy. White race was associated with increased rates of surgical candidacy compared with Black race (46.6% versus 77.2%; P < 0.0001). Compared with White patients, Black patients presented with a longer symptom duration (11.07 versus 6.99 years; P < 0.001), had a higher body mass index (mean, 34.5 versus 28.1; P < 1 × 10 -10 ), had a higher International Society of Lymphology stage ( P < 0.05), and were less likely to have maximized medical treatment for lymphedema (30.8% versus 55.4%; P < 0.01). CONCLUSIONS: This study demonstrates racial disparities in patients seeking physiological surgical treatment for lymphedema. Black patients present later with more severe disease, receive less nonsurgical treatment before consultation, and are less likely to meet criteria for physiological surgery. Improved patient and provider education on lymphedema and appropriate diagnosis and nonsurgical treatment is of primary importance to address this disparity.

Staphylococcal Toxic Shock Syndrome in a Burned Child Treated with an Antimicrobial Foam Dressing: A Case Report.

Staphylococcal toxic shock syndrome (TSS) is a severe systemic disease characterized by fever, hypotension, desquamating rash, and multiorgan dysfunction. Attributed to bacterial exotoxins, TSS has been a known, though rare, complication in the field of pediatric burns for decades. The adoption of new antimicrobial burn dressings has allowed for the management of small to medium sized burns with minimal discomfort or inconvenience to the patient. In this report, we discuss a 3-year-old male with burns wounds dressed using a silver-impregnated foam who went on to develop TSS.

Notch signaling: Its essential roles in bone and craniofacial development.

Notch is a cell-cell signaling pathway that is involved in a host of activities including development, oncogenesis, skeletal homeostasis, and much more. More specifically, recent research has demonstrated the importance of Notch signaling in osteogenic differentiation, bone healing, and in the development of the skeleton. The craniofacial skeleton is complex and understanding its development has remained an important focus in biology. In this review we briefly summarize what recent research has revealed about Notch signaling and the current understanding of how the skeleton, skull, and face develop. We then discuss the crucial role that Notch plays in both craniofacial development and the skeletal system, and what importance it may play in the future.

Stem cell therapy for chronic skin wounds in the era of personalized medicine: From bench to bedside.

With the significant financial burden of chronic cutaneous wounds on the healthcare system, not to the personal burden mention on those individuals afflicted, it has become increasingly essential to improve our clinical treatments. This requires the translation of the most recent benchtop approaches to clinical wound repair as our current treatment modalities have proven insufficient. The most promising potential treatment options rely on stem cell-based therapies. Stem cell proliferation and signaling play crucial roles in every phase of the wound healing process and chronic wounds are often associated with impaired stem cell function. Clinical approaches involving stem cells could thus be utilized in some cases to improve a body's inhibited healing capacity. We aim to present the laboratory research behind the mechanisms and effects of this technology as well as current clinical trials which showcase their therapeutic potential. Given the current problems and complications presented by chronic wounds, we hope to show that developing the clinical applications of stem cell therapies is the rational next step in improving wound care.

The wonders of BMP9: From mesenchymal stem cell differentiation, angiogenesis, neurogenesis, tumorigenesis, and metabolism to regenerative medicine.

Although bone morphogenetic proteins (BMPs) initially showed effective induction of ectopic bone growth in muscle, it has since been determined that these proteins, as members of the TGF-ß superfamily, play a diverse and critical array of biological roles. These roles include regulating skeletal and bone formation, angiogenesis, and development and homeostasis of multiple organ systems. Disruptions of the members of the TGF-ß/BMP superfamily result in severe skeletal and extra-skeletal irregularities, suggesting high therapeutic potential from understanding this family of BMP proteins. Although it was once one of the least characterized BMPs, BMP9 has revealed itself to have the highest osteogenic potential across numerous experiments both in vitro and in vivo, with recent studies suggesting that the exceptional potency of BMP9 may result from unique signaling pathways that differentiate it from other BMPs. The effectiveness of BMP9 in inducing bone formation was recently revealed in promising experiments that demonstrated efficacy in the repair of critical sized cranial defects as well as compatibility with bone-inducing bio-implants, revealing the great translational promise of BMP9. Furthermore, emerging evidence indicates that, besides its osteogenic activity, BMP9 exerts a broad range of biological functions, including stem cell differentiation, angiogenesis, neurogenesis, tumorigenesis, and metabolism. This review aims to summarize our current understanding of BMP9 across biology and the body.