New research reveals potential treatment to delay and manage osteoarthritis

November 12, 2020

Philadelphia, November 12, 2020 - Osteoarthritis (OA), a widely acknowledged cause of disability that affects patients' quality of life and has significant economic impact through healthcare costs and loss of earnings. In a novel study researchers have identified cytoplasmic localized histone deacetalyse 6 (HDAC6) as a promising therapeutic target to postpone development of and possibly treat OA using the HDAC6 inhibitor Tubastatin A. They report their results in The American Journal of Pathology, published by Elsevier.

"Because chondrocytes are the only resident cells in articular cartilage, the steady state of these cells is important to maintain joint function," explained lead investigator Weiyang Gao, MD, Department of Hand and Plastic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, PR China. "In various OA diseases, chondrocytes undergo a series of pathophysiologic changes, leading to the loss of chondrocytes, which can impair mitochondrial function and extracellular matrix synthesis (ECM) to promote the progression of OA."

Investigators detected the variations in expression level of HDAC6 after destabilization of the medial meniscus (DMM)-induced mouse OA model. They dissected the knee cartilage tissue of two-week-old mice to obtain primary chondrocytes. HDAC6 was up-regulated after OA and peaked at four weeks post-DMM. Thus, they constructed primary chondrocytes overexpressing HDAC6 by transfection of plasmid.

Their results indicate that overexpression of HDAC6 causes mitochondrial dysfunction and promotes reactive oxygen species production, leading to ECM degradation. However, the administration of the selective HDAC6 inhibitor Tubastatin A reversed the effect caused by HDAC6 overexpression in vitro and further postponed the progression of OA in vivo by ameliorating the degradation of cartilage and improving the microenvironment and function of the joint, suggesting that HDAC6 may be a target for delaying and managing OA with Tubastatin A.

"To our knowledge this is the first study to show that the expression level of HDAC6 is up-regulated in chondrocytes during the OA process and that the up-regulated expression of HDAC6 is associated with mitochondrial disfunction and ECM degradation," commented Dr. Gao. "Our results show that HDAC6 is a potential target for treatment of OA and supports the administration of Tubastatin A to treat OA."

OA is an inflammatory disease characterized by increased degradation of cartilage tissue in the joint due to overproduction of enzymes degrading the extracellular matrix. It is the most common joint disorder in the United States and is highly prevalent around the world. Among US adults 60 years of age and older the prevalence of symptomatic knee OA is approximately 10 percent in men and 13 percent in women. Chondrocytes are the only resident cells of articular cartilage, and the steady state of their intracellular environment is of great significance for maintaining the articular cartilage morphology.
-end-


Elsevier

Related Osteoarthritis Articles from Brightsurf:

Major savings possible with app-based osteoarthritis treatment
Osteoarthritis treatment conducted digitally via an app costs around 25% of what conventional care costs, according to a study from Lund University in Sweden published in the research journal PLOS ONE.

New approach to treating osteoarthritis advances
Injections of a natural 'energy' molecule prompted regrowth of almost half of the cartilage lost with aging in knees, a new study in rodents shows.

Bone drug may be beneficial for knee osteoarthritis
Bisphosphonates (a class of drugs that prevent the loss of bone density and used to treat osteoporosis and similar diseases) appear to be safe and beneficial for osteoarthritis patients.

Certain jobs linked to higher risk of knee osteoarthritis
Workers in jobs that typically involve heavy lifting, frequent climbing, prolonged kneeling, squatting, and standing face an increased risk of developing knee osteoarthritis.

App helps reduce osteoarthritis pain
By performing a few simple physical exercises daily, and receiving information about their disease regularly, 500 osteoarthritis patients were able to on average halve their pain in 6 months -- and improve their physical function.

Osteoarthritis can increase your risk for social isolation
In a study published in the Journal of the American Geriatrics Society, researchers examined information from the European Project on OSteoArthritis (EPOSA) study.

High rates of opioid prescriptions for osteoarthritis
Opioids work against severe pain but the risks of side effects and addiction are high.

Disease burden in osteoarthritis is similar to rheumatoid arthritis
Osteoarthritis (OA) has traditionally been viewed as a highly prevalent but milder condition when compared with rheumatoid arthritis (RA), and some may believe that it is part of a normal aging process requiring acceptance, not treatment.

3D printing may help treat osteoarthritis
In a Journal of Orthopaedic Research study, scientists used 3D printing to repair bone in the joints of mini-pigs, an advance that may help to treat osteoarthritis in humans.

Finger joint enlargements may be linked to knee osteoarthritis
Heberden's nodes (HNs) are bony enlargements of the finger joints that are readily detectable in a routine physical exam and are considered hallmarks of osteoarthritis.

Read More: Osteoarthritis News and Osteoarthritis Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.