Recent discoveries provide new treatment for osteoarthritis

As a new treatment for osteoarthritis, electric field stimulation reduces inflammation, restores cartilage

The degenerative joint disease osteoarthritis (OA) affects millions of patients. The underlying causes of OA are inflammation and excessive apoptosis (programmed death) of chondrocytes, the cells whose main function is to maintain healthy cartilage. Two recent major scientific discoveries have revolutionized our understanding of pain management and OA treatment — as a new treatment for osteoarthritis, the electric field stimulation (EFS) effects on cartilage inflammation and the effects of thermal stimulation (TS) on chondrocytes’ apoptosis include:

• The electric field stimulation activates the anti-inflammatory “adenosine – A2aR signaling pathway,” which downregulates joint inflammation and promotes restoration of the cartilage.
• Thermal stimulation significantly inhibits chondrocytes’ apoptosis and promotes anabolic (restorative) activities of the cartilage.

Newly developed technology, based on the latest medical discoveries, synergistically combines EFS and TS for pain management and treatment of OA. With this technology, EFS is carried into the treatment zone (cartilage) by pulsed magnetic field (MF) produced by electromagnetic coils. Inside the cartilage, the pulsed MF is converted into EF pulses that interact with chondrocytes and activate adenosine – A2aR pathway.

Inflammation and excessive apoptosis — root causes of disease

Osteoarthritis is a degenerative joint disease associated with damage to the articular cartilage and surrounding tissues and characterized by pain, stiffness and loss of function.

Articular cartilage is the smooth white tissue that covers the surface of all synovial joints in the human body. Its main function is to facilitate the movement of one bone against another. The cartilage contains specialized cells called chondrocytes that produce an extracellular matrix composed of collagen and proteoglycans.

Cartilage is one of the few tissues in the body that does not have its own blood supply and nerves. For nutrition and waste products’ release, chondrocytes depend on diffusion helped by the pumping action generated by compression of the cartilage.

In healthy cartilage, mitosis and apoptosis are balanced and an adequate number of chondrocytes is maintained; the apoptosis is low and apoptotic cells are quickly cleared by macrophages without causing inflammation.

Significantly influenced by inflammation, the natural history of osteoarthritis is manifested by steady decline of cartilage cellularity, degradation of cartilage matrix and surrounding tissues, and chronic pain.

Chronic inflammation and excessive apoptosis are two underlying mutually supportive causes of OA. For a successful treatment of OA, both of them must be targeted.

Newly-discovered natural regulator of inflammation: adenosine – A2aR pathway

Adenosine is a purine nucleoside generated by metabolically stressed or inflamed tissues that recently was recognized as a major endogenous anti-inflammatory regulator.

Under normal conditions, adenosine is continuously released from cells as a product of ATP degradation. Adenosine concentration in extracellular space is controlled by an enzyme called adenosine deaminase (ADA) which breaks it down and keeps the concentration level in high-nanomolar to low-micromolar range.

However, during conditions of stress, such as inflammation, levels of extracellular adenosine rise dramatically (up to 200 times). Adenosine regulates the function of both the innate and adaptive immune systems through targeting virtually every cell type that is involved in orchestrating the immune/inflammatory response. This broad action of anti-inflammatory adenosine – A2aR signaling pathway is a result of the predominant expression of A2aRs on all immune and parenchymal cells including chondrocytes.

Assisting the immune response

Adenosine – A2aR pathway activation inhibits early and late events occurring during an immune response, which include immune cell trafficking and proliferation, proinflammatory cytokine production, and cytotoxicity.

In the late stage, in addition to limiting inflammation, adenosine – A2aR pathway participates in tissue remodeling and restoration. Developing a means for activation of adenosine – A2aR pathway in chondrocytes would be highly beneficial for treatment of OA.

A new treatment for osteoarthritis: electric field stimulation reduces inflammation in OA

It is well established that natural wound healing involves generation of endogenous electric field stimulation (EFS). Recently a new treatment for osteoarthritis has been discovered where the endogenous EF also controls the processes of healing and remodeling bones and cartilages.

Exogenous EFS has been suggested for treatment of OA. In this case the therapeutic EF is carried into the treatment zone (cartilage) by pulsed magnetic field (MF) produced by a set of electromagnetic coils located outside the body. During a treatment session, the EFS more than doubles concentration of A2aRs on the cell surface and potentiates the downstream signal four times above the base level.

Adenosine – A2aR signaling pathway stimulates anti-inflammatory and anabolic (restorative) activities of chondrocytes; it accelerates natural healing of cartilage and subchondral bones and reduces pain by suppressing production of pain mediator prostaglandin E2.

Multiple studies have demonstrated effectiveness and safety of pulsed EFS therapy in suppressing inflammation in osteoarthritis.

Thermal stimulation blocks apoptosis of chondrocytes

Thermal stimulation (TS) of the joint increases blood flow around articular cartilage, promotes diffusion of nutrients and removal of the waste products, and partially reduces pain. But the most important aspect of using HS for OA is the generation of so called “heat shock proteins” (HSPs).

HSPs play numerous roles in cell function, including modulating protein activity, regulating protein degradation, facilitating protein translocation across organelle membranes, etc. The fundamental biological function of HSPs is to preserve cell survival by maintaining the vital functions of proteins and protecting cells against apoptosis.

Notably in this new treatment for osteoarthritis, improved protein function leads to a 4- to 7-fold increase in chondrocyte metabolism and production of the extracellular cartilage matrix, that significantly accelerates repair of cartilage.

TS can be synergistically combined with EFS. EFS prevents HSPs degradation by inhibiting adenosine deaminase (ADA) activity thus promoting accumulation of HSPs in the cells. In practical terms, HSPs can be induced by local thermal stimulation with temperatures 39-41 degrees Celsius for 10-30 minutes. After a session of TS, the concentration of HSPs stays elevated for 72 hours. This points to the optimal regimen of treatment at least three times per week.

The main therapeutic target of TS is apoptosis. The TS inhibits apoptosis and decreases secondary necrosis – the main proinflammatory stimulus that fuels inflammation in OA.

Reducing inflammation, blocking apoptosis, and promoting cartilage restoration

Historically, PEMF (Pulsed Electromagnetic Field) devices were promoted for having high magnetic fields, which runs contrary to the established research, because the active agent that provides biological effects is electric, not magnetic field.

Another issue is that the distribution of electric field in and around an electro-magnetic coil is significantly different from that of a magnetic field: In the center of every coil where the magnetic field is at maximum, the electric field is zero and has very low values around it, comprising a “dead zone” where no therapy is delivered. Another problem is that the cartilage in joints is a thin layer of tissue located between two bones. Bones have several times higher electrical resistivity than cartilage. If the EF, applied to the cartilage, crosses the adjacent bones, only a small fraction of EF is delivered into the cartilage; the rest goes to the bones.

The newest systems overcome this drawback, with a design to generate high EF and deliver it into the discs and facet joints in the plane of the cartilages, which allows avoiding losses of EF to the dead zones or adjacent bones.

JOHN A. MOROZ is president and CEO of BioMagnetic Sciences LLC, which provides non-invasive, long-term pain relief from joint inflammation with a patented medical device, the NovoPulse®, that improves daily function and performance, creating pain-free living. For the first time both inflammation reduction and tissue restoration are addressed using a combination of electrical and thermal stimulation. The NovoPulse® is a true breakthrough in pain management. Learn more at novo-pulse.com.