LMK-235 suppresses osteoclastogenesis and promotes osteoblastogenesis by inhibiting HDAC4.

Osteoblasts and osteoclasts play an important role in maintaining the structural integrity of bone tissue, in which osteoclasts degrade bone structure and osteoblasts restore bone tissue. The imbalance of osteoblast and osteoclast function can lead to many bone-related diseases, such as osteoporosis and inflammatory osteolysis. The drug that can both promote bone formation and inhibit bone loss will be able to treat those diseases.

mPPTMP195 nanoparticles enhance fracture recovery through HDAC4 nuclear translocation inhibition.

Delayed repair of fractures seriously impacts patients' health and significantly increases financial burdens. Consequently, there is a growing clinical demand for effective fracture treatment. While current materials used for fracture repair have partially addressed bone integrity issues, they still possess limitations.

FTY720 Attenuates LPS-Induced Inflammatory Bone Loss by Inhibiting Osteoclastogenesis via the NF-B and HDAC4/ATF Pathways.

Osteoclast (OC) abnormalities lead to many osteolytic diseases, such as osteoporosis, inflammatory bone erosion, and tumor-induced osteolysis. Exploring effective strategies to remediate OCs dysregulation is essential. FTY720, also known as fingolimod, has been approved for the treatment of multiple sclerosis and has anti-inflammatory and immunosuppressive effects.

A novel therapeutic strategy for cartilage diseases based on lipid nanoparticle-RNAi delivery system.

Background: Cartilage degeneration affects millions of people but preventing its degeneration is a big challenge. Although RNA interference (RNAi) has been used in human trials via silencing specific genes, the cartilage RNAi has not been possible to date because the cartilage is an avascular and very dense tissue with very low permeability.

Purpose: The objective of this study was to develop and validate a novel lipid nanoparticle (LNP)-siRNA delivery system that can prevent cartilage degeneration by knocking down specific genes.

Cyclic Equibiaxial Tensile Strain Alters Gene Expression of Chondrocytes via Histone Deacetylase 4 Shuttling.

Objectives: This paper aims to investigate whether equibiaxial tensile strain alters chondrocyte gene expression via controlling subcellular localization of histone deacetylase 4 (HDAC4).

Materials And Methods: Murine chondrocytes transfected with GFP-HDAC4 were subjected to 3 h cyclic equibiaxial tensile strain (CTS, 6% strain at 0.25 Hz) by a Flexcell® FX-5000™ Tension System.

Compression regulates gene expression of chondrocytes through HDAC4 nuclear relocation via PP2A-dependent HDAC4 dephosphorylation.

Biomechanics plays a critical role in the modulation of chondrocyte function. The mechanisms by which mechanical loading is transduced into intracellular signals that regulate chondrocyte gene expression remain largely unknown. Histone deacetylase 4 (HDAC4) is specifically expressed in chondrocytes.

Intra-Articular Injection of Cross-Linked Hyaluronic Acid-Dexamethasone Hydrogel Attenuates Osteoarthritis: An Experimental Study in a Rat Model of Osteoarthritis.

Cross-linked hyaluronic acid hydrogel (cHA gel) and dexamethasone (Dex) have been used to treat knee osteoarthritis (OA) in clinical practice owing to their chondroprotective and anti-inflammatory effects, respectively. The aim of the present study was to compare the treatment effects of the cHA gel pre-mixed with/without Dex in a surgery-induced osteoarthritis model in rats. Anterior cruciate ligament transection (ACLT) surgery was performed on the right knee of rats to induce OA.

Cartilage oligomeric matrix protein and hyaluronic acid are sensitive serum biomarkers for early cartilage lesions in the knee joint.

The purpose of this study was to evaluate the relationship between five previously established serum osteoarthritis biomarkers and the severity of cartilage lesions in the knee. Cartilage damage (classified according to the Outerbridge scoring system) and serum concentrations of cartilage oligomeric matrix protein (COMP), collagen type II C-telopeptide (CTX-II), matrix metalloproteinase-3 (MMP-3), collagen type III N-propeptide, (PIIINP), and hyaluronic acid (HA) were determined in 79 patients who underwent knee arthroscopy or total knee replacement. HA and COMP concentrations were significantly higher in the Outerbridge score 1 and 2 groups, respectively.

[Progress on prevention for anterior knee pain after primary total knee arthroplasty].

Total knee arthroplasty (TKA) identified as an effective treatment for ultimate knee joint disease can effectively relieve pain, correct deformity, improve knee function and enhance the quality of life of patients. Patient satisfaction has been increasingly considered as an important factor in evaluating the success of primary TKA. Anterior knee pain that usually appears in the region of the anterior knee is a recognized complaint for primary TKA and has a strong impact on the improvement of knee function and patient satisfaction of primary TKA.

Indian hedgehog in synovial fluid is a novel marker for early cartilage lesions in human knee joint.

To determine whether there is a correlation between the concentration of Indian hedgehog (Ihh) in synovial fluid (SF) and the severity of cartilage damage in the human knee joints, the knee cartilages from patients were classified using the Outer-bridge scoring system and graded using the Modified Mankin score. Expression of Ihh in cartilage and SF samples were analyzed with immunohistochemistry (IHC), western blot, and enzyme-linked immunosorbent assay (ELISA). Furthermore, we detected and compared Ihh protein levels in rat and mice cartilages between normal control and surgery-induced osteoarthritis (OA) group by IHC and fluorescence molecular tomography in vivo respectively.

[Treatment of adult early femur head necrosis with the tantalum screw].

Objective: To investigate a new method for the treatment adult early femur head necrosis in order to avoid further collapse and necrosis and improve the clinical symptoms.

Methods: From January 2009 to June 2010, 10 hips of 9 patients, including 7 males and 2 females, aged from 29 to 63 years old (averaged 44.1), with femur head necrosis were treated with implantation of the tantalum screw.