Mitochondria and Osteoarthritis: An Exciting New Frontier

A growing body of evidence is about to impact our understanding of degenerative joint disease and osteoarthritis in ways never before imagined. In the last few years, researchers have been delving with intense interest into the topic of mitochondria, cartilage, and degenerative joint disease. The information found opens up the door to a completely new perspective on joint health. The scenario of “which came first, the chicken or the egg?” is being re-defined in arthritis.

The Early Findings on Osteoarthritis

The first known medical publication on mitochondria and cartilage showed up in 1948, followed by a decade of silence. Then in the late 1950’s and early 1960’s work began on identifying what cartilage looked like underneath an electron microscope. Scientists did the early work of identifying what structures were seen in the chondrocytes or cartilage cells studying joint cartilage obtained from rabbits. One of the numerous components found in the middle layer of cartilage cells were mitochondria. Three general layers of cartilage were identified – superficial, middle, and deep. When degenerative joint disease was found in the tissue sample, it was the deep and middle layers that showed degenerative changes. In these tissue samples with osteoarthritis, the mitochondria structure appeared distorted and swollen. The deeper cartilage layer showed that the mitochondrial structure was starting to disintegrate and was often hard to identify the structure because of how badly damaged it was. The presence of the mitochondria was noted with very little understanding of its function. It was also identified in these early microscopic studies that very little blood supply occurred within cartilage.

Later in 1968, a study reviewed the structure of cartilage cells in human joint cartilage from samples taken from adults ages 37 to 83. The mitochondria in cartilage obtained also showed differences just like the earlier animal studies. Some mitochondria were healthy, others were swollen and distorted, and yet tissue samples showed that the mitochondria and chondrocytes were breaking down together. Like the studies with rabbit cartilage, glycogen stores were found next to mitochondria cells. Glycogen is the stored form of glucose. The purpose of mitochondria in the cartilage cells was determined to be like that in other tissues of the body and “being concerned in the production of energy-rich substances for use in biochemical processes”. The scientists noted that glycogen deposits in chondrocytes “probably serve as readily available source of raw material for biochemical processes”.

In this early study, one of the tissue samples that showed cartilage cell degeneration showed excessive destruction of mitochondria. The authors’ conclusion on this finding was: “One cannot however, assign a matrix-degrading role (breakdown of mitochondria) to bodies solely on the basis of their morphology (appearance). They may well be merely a secondary feature of osteoarthritis, and play no major part in its pathogenesis.” Their main focus was the damage and loss of chondrocytes. They attributed the loss of cartilage cells as the primary reason why osteoarthritis occurred. Mitochondria breakdown was dismissed or considered an after effect of cartilage cell deterioration.

A Dynamic View of Mitochondria and Cartilage Increases

Fast forward a few decades and we see new information on the horizon. The early findings and explanation of degenerative joint disease, chondrocytes and mitochondria is like looking at the Grand Canyon from only one direction. Scientists have expanded this into a panoramic view and the results are fascinating. Here are some of the more recent findings.

By 2004, the viewpoint on mitochondria and cartilage had expanded. Researchers believed that it was depletion of cartilage cell energy that caused degenerative joint disease. It had been identified that healthy cartilage cells require a healthy balance of energy production and energy use to maintain its integrity. Cartilage cells do this with a process called anaerobic glycolysis, i.e. glucose is broken down without using oxygen. In doing so, mitochondria provided back-up energy production for the cartilage cells. When energy was depleted, it triggered stress responses and inflammation as seen by the markers TNF-a, and IL-1, etc. This caused high amounts of nitric oxide to be released leading to cartilage cell death and damaged mitochondria. When the mitochondria were damaged, calcium was released and triggered cartilage cells to become calcified. Further research was built on top of this knowledge.

Updated research in 2009 revealed what a typical profile of mitochondria look like in osteoarthritis. Changes in energy production, damage to the mitochondrial membrane, and high levels of free radicals existed with trouble quenching and detoxifying them were found. In particular, the major mitochondrial antioxidant protein manganese-superoxide dismutase (SOD2) was deficient. The insufficient manganese SOD re-dox agent, a powerful antioxidant, could not protect the mitochondria leading to high levels of ROS production. The mitochondria and cartilage cells were damaged because of the loss of the powerful redox agent (antioxidant-like) protector of manganese dependent SOD.

October 2013 research expands on a common finding about degenerative arthritis development with acute trauma or chronic, cumulative stress. This is nothing new at first glance. The scientists viewed cellular models and humans with osteoarthritis in their ankles. The researchers took their studies further. Cellular studies showed that when cartilage was loaded (joints compressed and overloaded), the excessive load stressed the mitochondria in the cartilage cells. The mitochondria then released powerfully damaging free radicals, reactive oxygen species (ROS). ROS then caused the cartilage cells to die and the surrounding matrix to breakdown. When the surrounding tissue broke down, it caused a release of other inflammatory compounds to be released perpetuating the breakdown process. The end result was progressive cartilage loss. The stress response started with the mitochondria and end result was cartilage changes. Changing and relieving the mechanical stress thru traction and improved joint motion relieved pain and improved joint function in patients with end-stage post-traumatic osteoarthritis. This mechanical relief support is why exercise and physical medicine is so important for managing degenerative joint disease.

Mitochondria Release Damaging MMPs

Information found in a 2014 study showed that when mitochondria were injured and mitochondria DNA damage occurred, free radicals (ROS) were released. This damage caused a massive release of MMPs (matrix metalloproteinases). High levels of MMPs are hallmark of osteoarthritis progression. Scientists have known that high levels of MMPs are characteristic of osteoarthritis and joint damage, but they didn’t have the connection that mitochondria damage led to elevated MMPs levels. The MMPs elevate in response to mitochondria damage. The MMPs then provoke more inflammation and cause more tissue destruction with the chondrocytes. This again changed the chicken versus egg picture with MMPs.

Advanced Glycation End Products (AGEs)

In the early studies that identified cell structure, scientists found storage sites of glucose next to mitochondria in the cartilage cells. While some of it may essential for mitochondrial energy production, too much glucose build-up is detrimental. Over the years, researchers found that Advanced Glycation End (AGEs) products and imbalanced leptin worsen degenerative joint disease. AGEs are the result of dysfunctional excess blood sugar and lead to many degenerative diseases like diabetes, heart disease, and Alzheimer’s disease. AGEs occur when glucose binds onto proteins in a process called glycation. This bond makes cells stiffer, ages faster, and cells are more susceptible to damage.

Know Your A1C Number

AGEs is directly related with your blood sugar levels. The simple blood test, hemoglobin A1C or glycated hemoglobin test measures how much your hemoglobin is coated with blood sugar. It essentially tells you how well you are managing your blood sugar over the course of the previous two to three months. Standard medical interpretation is that a level of 6.5 percent and higher means that you have diabetes. A result between 5.7 to 6.4 percent means that you are pre-diabetic. More recent research from the New England Journal of Medicine confirms that a hemoglobin A1C over 5.5 is known to cause neurodegeneration and increase the risk for Alzheimer’s disease and many other diseases. Expand the picture now to cartilage cells.

A1C, AGEs, Mitochondria, and Cartilage

In February 2015, researchers reported on a connection between AGEs, mitochondria and cartilage breakdown. They found that AGEs caused cartilage cells to die. Simultaneously it caused increased free radical damage from reactive oxygen species (ROS) and other damaging compounds (caspace-3) and reduced energy production interfering with mitochondria function. Remember the ROS free radicals? They are released with mitochondrial damage. The AGEs ended up damaging the mitochondria, depleting energy within the cartilage cells, invoking inflammation and eventually causing cartilage cells to die. In this study, the authors found that one compound stopped this AGEs mitochondrial injury and cartilage cell death. It was the nutrient N-acetyl cysteine (NAC).

Cellular Clean-Up and Mitochondria

In April 2015 autophagy problems were also identified in degenerative joint disease and mitochondria. Autophagy is the process where old, worn-out cells are removed, so new cells can come in and restore cell function. It’s out with the old and in with the new. When the clean-up process was dysfunctional, additional mitochondria dysfunction occurred and cartilage cells broke down. This is yet another problem perpetuating mitochondria deterioration that advances breakdown in the cartilage cells.

AMPK and Mitochondria

Additional information identified May 2015, showed that cartilage cells improve with AMPK-enzyme activity. This is the master enzyme switch that turns on the birth of mitochondria or mitochondria biogenesis. When this switch is defunct, mitochondria biogenesis becomes deficient and cartilage cells breakdown. When the AMPK enzyme is activated, the processed is reversed and the damage to cartilage cells is averted. Exercise is one activity that turns on AMPK. This is yet another reason why exercise and movement is so beneficial for arthritis problems.

We know that many disorders like obesity, fibromyalgia, Chronic Fatigue Syndrome, cancer, and diabetes etc. are linked with AMPK dysfunction. Often, individuals who suffer from these disorders have debilitating arthritis not related to trauma or occupational stress. This information of AMPK, mitochondria and cartilage helps to open the door for complex disorders that are seemingly unrelated or considered a consequence of aging.

What Does This All Mean?

This article provides a brief outline of our knowledge on mitochondria and arthritis. So what does this all mean? Mitochondria support is imperative to aging well and healthy joints. Mitochondria are involved with energy production and need to support the cartilage cells. In order to accomplish this, the mitochondria need enough antioxidants to buffer the reactive oxygen species (ROS) or free radicals to maintain homeostasis within cartilage. When this antioxidant buffer is exhausted or weak, then inflammatory chemicals are triggered by the free radicals. This causes the mitochondria to become dysfunctional, broken down and insufficient in number, eventually exhausting joint health and progressing into the slow onset of joint pathology.

Remember what was first identified in the initial cell studies? The middle and deep layers of cartilage tissue contain extensive mitochondria. When joint degeneration occurs, it starts from a central point deep within the middle and deep layers of cartilage cells and progresses outward. The early stage of this process is called chondropenia for decreased number of cartilage cells. Further progression of chondropenia leads to the end result where cartilage cells breakdown, die, and cause more inflammation within the joint tissues and leads to end stage pathology, i.e. bone on bone, joint replacement surgery, or severe disability and severe osteoarthritis. As we found, several things amplify this entire path of mitochondrial and cartilage cell breakdown. These include acute and chronic repetitive stress-trauma, obesity, and blood sugar problems.

Information is presently doubling every 12 months. This brief reflection points out a lot of missing pieces and can be readily combined with what we do know about joint health. Historically, the focus on arthritis has been to support cartilage cells with nutrients like glucosamine and chondroitin. Many individuals find great benefit and this is one dimension of keeping cartilage cells healthy.

We also know that when cartilage cells fail to have the right type of fat present, then the other non-beneficial fat stored in cartilage cells ultimately cause the release of arachidonic acid. Too much arachidonic acid or omega-6 oils in the diet puts the body into a pro-inflammatory state. Adequate healthy omega-3 oils provide protection and healthy lubrication to joints.

Cartilage cells not only need good fats to keep the tissue lubricated and protected, they also need adequate hydration. Once cartilage dries out from inflammation, it tears and breakdowns more rapidly.

Adding mitochondria support to cartilage support provides a foremost change in supportive options. It will take many years for this information to make it into mainstream medicine and into your doctor’s office as a standard treatment. It takes about 17 years for doctors to change their practice patterns from the time that credible new research information is presented. Combine this with the rate of information doubling every 12 months; it will be like trying to turn a ship locked in ice in the dead of winter. It means that you need to be in charge of your health.

For those who have marginally responded or failed to respond to traditional nutritional support or medical support, this new breakthrough understanding may just open up remarkable doors. This is especially true for those who also struggle with other symptoms of mitochondria dysfunction. As with any situation, prevention and support at the sign of early signs of distress provide more profound support rather than at complete joint destruction. Several nutrients and antioxidants protect mitochondria, and support modulation of MMPs, autophagy, and AGEs. (Use the search bar on our website to learn about these resources.) Exercise and physical activity provides synergistic support to the mitochondria, AMPK, and AGEs. Getting leptin under control is fundamental as leptin protects cartilage cells from cumulative joint stress.

As information expands and grows in this field of mitochondria dysfunction, joint health and more, Wellness Resources aims to provide you with timely information. The fact that it can take the medical industry up to 17 years to change its standard of treatment means “Houston, we have a problem!” We cannot let this continue to be the case and watch the health of our nation fall apart. The good news is that you can take this information, learn from it, and be proactive.