Novel Effect of Hyaluronan and Proteoglycan Link Protein 1(HAPLN1) on Hair Follicle Cells Proliferation and Hair Growth

Hair loss is a common condition that can have a negative impact on an individual’s quality of life. The severe side effects and the low efficacy of current hair loss medications create unmet needs in the field of hair loss treatment. Hyaluronan and Proteoglycan Link Protein 1 (HAPLN1), one of the components of the extracellular matrix, has been shown to play a role in maintaining its integrity. HAPLN1 was examined for its ability to impact hair growth with less side effects than existing hair loss treatments. HAPLN1 was predominantly expressed in the anagen phase in three stages of the hair growth cycle in mice and promotes the proliferation of human hair matrix cells. Also, recombinant human HAPLN1 (rhHAPLN1) was shown to selectively increase the levels of transforming growth factor-β receptor II in human hair matrix cells. Furthermore, we observed concomitant activation of the ERK1/2 signaling pathway following treatment with rhHAPLN1. Our results indicate that rhHAPLN1 elicits its cell proliferation effect via the TGF-β2-induced ERK1/2 pathway. The prompt entering of the hair follicles into the anagen phase was observed in the rhHAPLN1-treated group, compared to the vehicle-treated group. Insights into the mechanism underlying such hair growth effects of HAPLN1 will provide a novel potential strategy for treating hair loss with much lower side effects than the current treatments.

A Novel Role of Hyaluronic Acid and Proteoglycan Link Protein 1(HAPLN1) in Delaying Vascular Endothelial Cell Senescence

Cardiovascular diseases (CVDs) are the most common cardiovascular system disorders. Cellular senescence is a key mechanism associated with dysfunction of aged vascular endothelium. Hyaluronic acid and proteoglycan link protein 1 (HAPLN1) has been known to non-covalently link hyaluronic acid (HA) and proteoglycans (PGs), and forms and stabilizes HAPLN1-containing aggregates as a major component of extracellular matrix. Our previous study showed that serum levels of HAPLN1 decrease with aging. Here, we found that the HAPLN1 gene expression was reduced in senescent human umbilical vein endothelial cells (HUVECs). Moreover, a recombinant human HAPLN1 (rhHAPLN1) decreased the activity of senescence-associated β-gal and inhibited the production of senescence-associated secretory phenotypes, including IL-1β, CCL2, and IL-6. rhHAPLN1 also downregulated IL-17A levels, which is known to play a key role in vascular endothelial senescence. In addition, rhHAPLN1 protected senescent HUVECs from oxidative stress by reducing cellular reactive oxygen species levels, thus promoting the function and survival of HUVECs and leading to cellular proliferation, migration, and angiogenesis. We also found that rhHAPLN1 not only increases the sirtuin 1 (SIRT1) levels, but also reduces the cellular senescence markers levels, such as p53, p21, and p16. Taken together, our data indicate that rhHAPLN1 delays or inhibits the endothelial senescence induced by various aging factors, such as replicative, IL-17A, and oxidative stress-induced senescence, thus suggesting that rhHAPLN1 may be a promising therapeutic for CVD and atherosclerosis.

Development of a Label-Free LC-MS/MS-Based Glucosylceramide Synthase Assay and Its Application to Inhibitors Screening for Ceramide-Related Diseases

Ceramide metabolism is known to be an essential etiology for various diseases, such as atopic dermatitis and Gaucher disease. Glucosylceramide synthase (GCS) is a key enzyme for the synthesis of glucosylceramide (GlcCer), which is a main ceramide metabolism pathway in mammalian cells. In this article, we developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to determine GCS activity using synthetic non-natural sphingolipid C8-ceramide as a substrate. The reaction products, C8-GlcCer for GCS, could be separated on a C18 column by reverse-phase high-performance liquid chromatography (HPLC). Quantification was conducted using the multiple reaction monitoring (MRM) mode to monitor the precursor-to-product ion transitions of m/z 588.6 → 264.4 for C8-GlcCer at positive ionization mode. The calibration curve was established over the range of 0.625–160 ng/mL, and the correlation coefficient was larger than 0.999. This method was successfully applied to detect GCS in the human hepatocellular carcinoma cell line (HepG2 cells) and mouse peripheral blood mononuclear cells. We also evaluated the inhibition degree of a known GCS inhibitor 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) on GCS enzymatic activity and proved that this method could be successfully applied to GCS inhibitor screening of preventive and therapeutic drugs for ceramide metabolism diseases, such as atopic dermatitis and Gaucher disease.

Paraquat Induces Apoptosis through a Mitochondria-Dependent Pathway in RAW264.7 Cells

Paraquat dichloride (N,N-dimethyl-4-4'-bipiridinium, PQ) is an extremely toxic chemical that is widely used in herbicides. PQ generates reactive oxygen species (ROS) and causes multiple organ failure. In particular, PQ has been reported to be an immunotoxic agrochemical compound. PQ was shown to decrease the number of macrophages in rats and suppress monocyte phagocytic activity in mice. However, the effect of PQ on macrophage cell viability remains unclear. In this study, we evaluated the cytotoxic effect of PQ on the mouse macrophage cell line, RAW264.7 and its possible mechanism of action. RAW264.7 cells were treated with PQ (0, 75, and 150 muM), and cellular apoptosis, mitochondrial membrane potential (MMP), and intracellular ROS levels were determined. Morphological changes to the cell nucleus and cellular apoptosis were also evaluated by DAPI and Annexin V staining, respectively. In this study, PQ induced apoptotic cell death by dose-dependently decreasing MMP. Additionally, PQ increased the cleaved form of caspase-3, an apoptotic marker. In conclusion, PQ induces apoptosis in RAW264.7 cells through a ROS-mediated mitochondrial pathway. Thus, our study improves our knowledge of PQ-induced toxicity, and may give us a greater understanding of how PQ affects the immune system.

Intramuscular Cyst of the Rotator Cuff Associated with Tear of the Rotator Cuff: A Case Report

Periarticular cysts in the shoulder joint are relatively rare. The most common are paralabral cysts, which can cause suprascapular nerve entrapment syndrome. Acromioclavicular juxtaarticular cysts have been described in association with full-thickness rotator cuff tears and a degenerated acromioclavicular joint. Intramuscular cysts of the rotator cuff are a relatively rare and unknown type of periarticular cyst. We report a case of an intramuscular cyst of the rotator cuff that was associated with a tear of the rotator cuff.

Common Misconceptions or Misdiagnosis in Shoulder Disorders / 대한류마티스학회지

Many patients, physicians and even orthopedic surgeons commonly have misconceptions about several shoulder disorders, so they misdiagnose these diseases and treat patients inappropriately. In this article, we describe some common misconceptions and misdiagnosis in shoulder disorders; such as rotator cuff disease, SLAP lesion, clavicle fracture et al. It will be helpful to understand how these disorders can be approached and managed.

Minimally Invasive vs. Standard Total Knee Arthroplasty : A Prospective Randomized Comparison Study / 대한정형외과학회잡지

PURPOSE: A prospective randomized study was performed to compare the clinical results of standard vs. minimally invasive TKA (MIS TKA), and to identify the preoperative factors that help to figure out the indications of MIS TKA. MATERIALS AND METHODS: Eighty patients with osteoarthritic knees were randomized to standard TKA and MIS TKA groups. The operations were performed by one senior author with the same TKA system. Preoperative evaluation included body mass index (BMI), range of motion (ROM), deformity, and WOMAC and Knee Society scores. Operative factors were evaluated, including length of skin incision, operation time, and operative complications. Postoperative evaluation was performed daily until discharge from hospital, at 1 month, 3 months, 6 months, and 1 year postoperatively, including blood loss, amount of epidural anesthesia, visual analog scale (VAS), ROM, possible day of active straight leg raising (SLR), possible day of discharge, complications, WOMAC and Knee Society scores, patient's satisfaction with the operative scar, and radiological evaluation. RESULTS: There were statistically significant differences in daily VAS, operation time, length of skin incision, and possible day of SLR (p<0.05). There were no significant differences in other clinical aspects that were compared in this study. Complications occurred only in MIS group; 1 partial tear of MCL and 1 fracture of lateral femoral condyle. Preoperative ROM or BMI was not correlated with longer operation time. Significantly longer operation time was observed when both the preoperative fixed flexion contracture and varus deformity were greater than 10 degrees, or one or both of them was greater than 15 degrees (p<0.05). CONCLUSION: MIS TKA has the advantage of less pain, shorter skin incision, and earlier possible SLR in the early postoperative period, but it requires a longer operation time and careful surgical technique. The surgeon should select the MIS procedure by carefully considering its advantages and disadvantages. Both the preoperative flexion contracture and varus deformity greater than 10 degrees, or one of them greater than 15 degrees seems to be the relative contraindication of MIS TKA from the result of this study.

Bilateral Total Knee Arthroplasties: Comparison of Simultaneous, Sequential, Staged Knee Replacement

PURPOSE: To compare the clinical outcomes of bilateral total knee arthroplasty (TKA) performed simultaneously by two teams or sequentially by one team under a single anesthesia, with those of staged bilateral TKA performed during separate hospitalizations. MATERIALS AND METHODS: We retrospectively analyzed 83 patients (166 knees) who underwent bilateral TKA. Group I comprised 25 patients receiving simultaneous bilateral TKA. Group II comprised 31 patients receiving sequential bilateral TKA. Group III comprised 27 patients receiving staged bilateral TKA spaced an average of 8.9 weeks apart. Data including complication rate, length of hospital stay, and allogenic blood transfusion rate were evaluated. RESULTS: Complication rate for group I, II, and III was 12%, 19.4%, and 25.9%, respectively, but there was no significant difference. Allogenic blood transfusion rate was 28%, 29%, and 11.1%, respectively, but there was no significant difference. The average hospital stay was 8.4 days, 8.9 days, and 14.5 days, respectively, and group I and II showed significantly shorter hospitalization compared with group III. CONCLUSION: Simultaneous or sequential bilateral TKA is a safe and efficient procedure that can shorten hospital stay without increasing complication rate and allogenic blood transfusion rate, compared with staged bilateral TKA.