Mocetinostat activates Krüppel-like factor 4 and protects against tissue destruction and inflammation in osteoarthritis.

Osteoarthritis (OA) is the most common joint disorder, and disease-modifying OA drugs (DMOADs) represent a major need in OA management. Krüppel-like factor 4 (KLF4) is a central transcription factor upregulating regenerative and protective functions in joint tissues. This study was aimed to identify small molecules activating KLF4 expression and to determine functions and mechanisms of the hit compounds.

Runx2 and Runx3 differentially regulate articular chondrocytes during surgically induced osteoarthritis development.

The Runt-related transcription factor (Runx) family plays various roles in the homeostasis of cartilage. Here, we examined the role of Runx2 and Runx3 for osteoarthritis development in vivo and in vitro. Runx3-knockout mice exhibited accelerated osteoarthritis following surgical induction, accompanied by decreased expression of lubricin and aggrecan.

Targeting FoxO transcription factors with HDAC inhibitors for the treatment of osteoarthritis.

Objectives: Osteoarthritis (OA) features ageing-related defects in cellular homeostasis mechanisms in articular cartilage. These defects are associated with suppression of forkhead box O (FoxO) transcription factors. FoxO1 or FoxO3 deficient mice show early onset OA while FoxO1 protects against oxidative stress in chondrocytes and promotes expression of autophagy genes and the essential joint lubricant proteoglycan 4 (PRG4).

Krüppel-like factor-4 and Krüppel-like factor-2 are important regulators of joint tissue cells and protect against tissue destruction and inflammation in osteoarthritis.

Objectives: Analysing expression patterns of Krüppel-like factor (KLF) transcription factors in normal and osteoarthritis (OA) human cartilage, and determining functions and mechanisms of KLF4 and KLF2 in joint homoeostasis and OA pathogenesis.

Methods: Experimental approaches included human joint tissues cells, transgenic mice and mouse OA model with viral KLF4 gene delivery to demonstrate therapeutic benefit in structure and pain improvement. Mechanistic studies applied global gene expression analysis and chromatin immunoprecipitation sequencing (ChIP-seq).

Unicompartmental knee arthroplasty is associated with lower proportions of surgical site infection compared with total knee arthroplasty: A retrospective nationwide database study.

Background: This study aimed to clarify the association between types of knee arthroplasty (KA) (total knee arthroplasty (TKA) or unicompatmental knee arthroplasty (UKA)) and surgical site infection (SSI) with adjustment for various factors, using a Japanese national database.

Methods: Data on 181,608 patients who underwent unilateral primary KA for osteoarthritis from 2010 to 2017 were obtained from the Japanese Diagnosis Procedure Combination database. SSI was identified based on International Classification of Diseases 10th Revision codes.

Type of bone graft and primary diagnosis were associated with nosocomial surgical site infection after high tibial osteotomy: analysis of a national database.

Purpose: Although several small-scale studies have reported risk factors for surgical site infection (SSI) after high tibial osteotomy (HTO), no study has collectively analysed risk factors in a large cohort. The present study aimed to clarify the risk factors for SSI after HTO using a national database.

Methods: Data of inpatients who underwent HTO from 2010 to 2017 were obtained from the Diagnosis Procedure Combination database in Japan.

Chronological Changes in Anterior Knee Stability after Anatomical Anterior Cruciate Ligament Reconstruction Using Bone-Patellar Tendon-Bone and Hamstring Grafts.

The clinical outcomes of anterior cruciate ligament (ACL) reconstruction are typically evaluated at specific time points only. This study aimed to characterize the chronological changes in anterior knee stability after anatomical ACL reconstruction and to compare the anterior knee stability achieved with bone-patellar tendon-bone (BPTB) and hamstring tendon (HT) grafts. A total of 59 patients underwent anatomical rectangular tunnel ACL reconstruction using the BPTB graft and 23 patients underwent anatomical double-bundle ACL reconstruction using the HT graft.

Simple and Robust Differentiation of Human Pluripotent Stem Cells toward Chondrocytes by Two Small-Molecule Compounds.

A simple induction protocol to differentiate chondrocytes from pluripotent stem cells (PSCs) using small-molecule compounds is beneficial for cartilage regenerative medicine and mechanistic studies of chondrogenesis. Here, we demonstrate that chondrocytes are robustly induced from human PSCs by simple combination of two compounds, CHIR99021, a glycogen synthase kinase 3 inhibitor, and TTNPB, a retinoic acid receptor (RAR) agonist, under serum- and feeder-free conditions within 5-9 days. An excellent differentiation efficiency and potential to form hyaline cartilaginous tissues in vivo were demonstrated.

Length of the Tendon within the Tibial Tunnel Affects Tibial Tunnel Widening following Anatomic Anterior Cruciate Ligament Reconstruction Using a Bone-Patellar Tendon-Bone Graft.

The purpose of this study was to retrospectively investigate the effects of variations in the length of the tendon within the tibial tunnel on tunnel widening (TW) following anatomical anterior cruciate ligament (ACL) reconstruction using a bone-patellar tendon-bone (BTB) graft. In total, 68 patients who underwent isolated ACL reconstructions using BTB grafts were included in this study. The patients were divided into two groups according to the length of the tendon within the tibial tunnel: group S ( = 30; tendon length, < 10 mm) and group L ( = 38; tendon length, ≥ 10 mm).

Meniscal bearing dislocation while rolling over in sleep following Oxford medial unicompartmental knee arthroplasty.

Meniscal bearing dislocation while rolling over in sleep has never been reported in Oxford unicompartmental knee arthroplasty (UKA). This study reports two cases of meniscal bearing dislocation into the intercondylar ridge while rolling over in sleep. In the case of one patient, closed reduction of the bearing was performed, and the use of a knee brace was effective in preventing re-dislocation.

Atopic dermatitis is a novel demographic risk factor for surgical site infection after anterior cruciate ligament reconstruction.

Purpose: Although various risk factors for surgical site infection after anterior cruciate ligament reconstruction (ACLR) have been reported, the number of studies with large sample sizes on this topic is limited. The aim of the present study was to clarify the risk factors for early surgical site infection after ACLR in a large cohort using a national database in Japan.

Methods: The data of patients who underwent ACLR from 2010 to 2015 were obtained from the Diagnosis Procedure Combination database, which covers approximately half of all hospital admissions in Japan.

Annual trends in arthroscopic meniscus surgery: Analysis of a national database in Japan.

Background: The importance of meniscus preservation is widely recognized. There have been a few studies describing trends in meniscectomy and meniscus repair in the United States; however, they presented differing results. We reported annual trends in meniscus surgery, using a national database in Japan.

Surgical timing of anterior cruciate ligament reconstruction to prevent associated meniscal and cartilage lesions.

Background: The purpose of this study was to analyze the association between the prevalence of meniscal and chondral lesions and the timing of surgery in patients undergoing primary anterior cruciate ligament (ACL) reconstruction to determine a safe time for surgery.

Methods: This retrospective study involved 226 patients (91 females and 135 males; median age, 29 years) undergoing primary ACL reconstruction. Time interval from ACL injury to surgery (median, 4 months; range, 1-420 months) and concomitant meniscal and cartilage lesions in ACL reconstruction were reviewed.

Annual trends in knee arthroplasty and tibial osteotomy: Analysis of a national database in Japan.

Background: Various nationwide studies have reported differing annual trends in utilization of knee arthroplasty and tibial osteotomy. Using the Diagnosis Procedure Combination database in Japan, the present series examined annual trends and demographics in total knee arthroplasty (TKA), unicompartmental knee arthroplasty (UKA) and tibial osteotomy.

Methods: All patients were identified who underwent TKA, UKA or tibial osteotomy for osteoarthritis, osteonecrosis or rheumatoid arthritis of the knee between July 2007 and March 2015.

Different regulation of limb development by p63 transcript variants.

The apical ectodermal ridge (AER), located at the distal end of each limb bud, is a key signaling center which controls outgrowth and patterning of the proximal-distal axis of the limb through secretion of various molecules. Fibroblast growth factors (FGFs), particularly Fgf8 and Fgf4, are representative molecules produced by AER cells, and essential to maintain the AER and cell proliferation in the underlying mesenchyme, meanwhile Jag2-Notch pathway negatively regulates the AER and limb development. p63, a transcription factor of the p53 family, is expressed in the AER and indispensable for limb formation.

Regulation of Chondrocyte Survival in Mouse Articular Cartilage by p63.

Objective: Transcription factor p63, of the p53 family, regulates cell proliferation, survival, and apoptosis in various cells and tissues. This study was undertaken to examine the expression and roles of p63 transcript variants in the mouse growth plate and articular chondrocytes.

Methods: For in vivo analyses, we generated Cre-mediated TAp63α-transgenic and TAp63γ-transgenic mice.

Ultrasound biomicroscopic findings of the iridocorneal angle in live healthy and glaucomatous dogs.

By using ultrasound biomicroscopy (UBM), the cross-sectional structures of the entire iridocorneal angle (ICA) which are unable to assess with gonioscopic examination were evaluated objectively and quantitatively in live healthy and glaucomatous dogs. The ICAs of normotensive eyes in healthy dogs with normal open angle (NOR), a predisposition to primary closed angle glaucoma (PCAG) (PREDIS) and suffering from unilateral PCAG (UNI), as well as the ICAs of hypertensive eyes with acute and chronic PCAG (ACG and CRG), were assessed. The opening of the ciliary cleft in PREDIS was smaller than that in NOR.

Hyaline cartilage formation and tumorigenesis of implanted tissues derived from human induced pluripotent stem cells.

Induced pluripotent stem cells (iPSCs) are a promising cell source for cartilage regenerative medicine. Meanwhile, the risk of tumorigenesis should be considered in the clinical application of human iPSCs (hiPSCs). Here, we report in vitro chondrogenic differentiation of hiPSCs and maturation of the differentiated hiPSCs through transplantation into mouse knee joints.

Transcription factor Hes1 modulates osteoarthritis development in cooperation with calcium/calmodulin-dependent protein kinase 2.

Notch signaling modulates skeletal formation and pathogenesis of osteoarthritis (OA) through induction of catabolic factors. Here we examined roles of Hes1, a transcription factor and important target of Notch signaling, in these processes. SRY-box containing gene 9 (Sox9)-Cre mice were mated with Hes1(fl/fl) mice to generate tissue-specific deletion of Hes1 from chondroprogenitor cells; this deletion caused no obvious abnormality in the perinatal period.

Recurrent hemarthrosis after total knee arthroplasty caused by the impingement of a remnant lateral meniscus: a case report.

A case of recurrent hemarthrosis initially presenting after the fifth postoperative month is described. Because of recurrent pain and swelling, the patient underwent an arthroscopy 14 months after total knee arthroplasty (TKA). A remnant posterior lateral meniscus was found to be impinged between the femoral component and the tibial liner, and there was oozing from the hypertrophied synovium around the remnant meniscus.

Evaluation of the distance between Schwalbe's line and the anterior lens capsule as a parameter for the correction of ultrasound biomicroscopic values of the canine iridocorneal angle.

Objective: To determine whether the distance between Schwalbe's line (the peripheral termination of Descemet's membrane, i.e., the borderline between the cornea and sclera) and the anterior lens capsule (SLD) is an applicable parameter for correcting raw ultrasound biomicroscopic values of the canine iridocorneal angle (ICA) and to establish a comparative system for the ICA values in different canine breeds with varied body sizes/weights.

Rectification of width and area of the ciliary cleft in dogs.

The width and area of the ciliary cleft (CCW and CCA) according to ultrasound biomicroscopy was rectified to compare dogs of different body sizes/weights, including toy breed (TBG), small breed (SBG), medium breed (MBG) and large/giant breed groups (LGBG). A linear correlation was detected between the natural log of body weight and the ocular axial length (OAL) reflecting the ocular size (OS; r=0.81, p<0.