The Pathophysiology Of Knee Osteoarthritis In Layman’s Terms | Guide For Nerds

Written By on June 13, 2022 — Medically Reviewed By Kris Ceniza (PT)

Written by on June 13, 2022 — Medically Reviewed By: Kris Ceniza (PT)

doctor seeing a knee X-ray

The pathophysiology of knee osteoarthritis is a deep dive into all the bodily processes that cause this condition. So, heads up – this article is for hardcore nerds without a medical background.

You’ll understand why this degenerative joint disease happens and the structures affected by it – in layman’s terms. See, my goal is to ensure you actually understand this already complex condition.

So, without further ado, these are the topics we’ll cover. Tap on any of them to go straight to each section:

Quick recap: What is knee OA?

Knee osteoarthritis is a degenerative joint disease. It may be asymptomatic for some while causing severe and limiting symptoms in others. (1)

There are different stages of OA and it often gets worse over time. Its two main causes are (2):

Now, the main difference between them is that one happens earlier than the other. But the bodily processes that cause the degeneration are the same. (3)

The 7 structures involved in the pathophysiology of knee OA

We used to think that this disease only affected the cartilage and that its degradation was mainly due to the wear and tear of the knee. But now we know there’s much more to the story.

It turns out that knee osteoarthritis affects the entire joint, not only the cartilage. And the tissues involved will determine the severity of the symptoms. (4)

This explains why some people have severe radiographic evidence of osteoarthritis but don’t have any symptoms. While others are still in the early stages and are experiencing extreme pain. (1)

Now, let’s take a look at each part of the knee joint and its role in this disease:

Knee Force Knee Sleeve

1) Articular cartilage

anatomic drawing of articular cartilage

The articular cartilage is a smooth, cushion-type tissue that covers the end of the bones, where they meet together to form the joints. It keeps the friction to a minimum so we can move freely.

It’s made of a type of cell called “chondrocyte,” responsible for rebuilding and repairing the cartilage.

Now, these cells are surrounded by a substance called “extracellular matrix” (ECM) made of water, collagen, proteins, and other compounds. It provides the nutrients the chondrocytes need to keep the cartilage healthy.

The cartilage doesn’t have blood vessels or nerves, though. This means that its only source of nutrients is the ECM. (4)

How does the articular cartilage stay healthy?

Through mechanotransduction. This is a process where an external load stimulates the cell, “telling” it to repair and rebuild itself.

In other words, the chondrocyte is capable of keeping articular cartilage degeneration at bay thanks to physical activity. Given at the right amounts, exercise stimulates the regenerative process of the tissue. (4)

And what causes it to wear off?

Major causes include lack of movement and an excess of it.

Insufficient mechanical stimuli – i.e. little to no physical activity – softens the articular cartilage. It’s as if it kept the chondrocytes “asleep.” They don’t know they have to repair the tissue, which weakens the cartilage and makes it prone to damage.

But excess load also wears it off. This is because the chondrocytes are overworking and deplete the nutrients in the ECM quickly. The cartilage isn’t able to repair itself at the rate it needs, thus causing irreversible damage. (4)

Over time, this leads to joint space narrowing – one of the diagnostic criteria for knee osteoarthritis.

Does this damage cause pain?

Contrary to popular belief, cartilage damage alone doesn’t cause knee pain.

As this tissue doesn’t have blood vessels or nerves, it can’t produce the chemicals or send the pain signals that ultimately lead to symptoms. (4, 5)

However, as the deterioration advances, it does affect other tissues that can cause pain and inflammation – like the ones described below. (5)

2) Subchondral bone

This is the bone tissue that’s right under the cartilage. It contains tons of blood vessels, which supply nutrients to the ECM to ultimately deliver them to the chondrocytes. (6, 7)

The interaction between the subchondral bone and the cartilage is fundamental for joint health. It also plays a pivotal role in the progression of osteoarthritis. (4)

See, knee OA makes the subchondral bone thicker than it should.

This is called “subchondral sclerosis.” It happens because something is triggering the creation of new bone tissue. The reason behind this isn’t fully understood, though. (4)

One hypothesis is that abnormal mechanical stimuli – i.e. excess or lack thereof – promote the formation of more subchondral bone.

The problem is that this new bone is weaker and prone to damage, forcing it to be in a constant state of repair. (6)

Ultimately, this regular breaking and repairing process produces chemicals that affect the cartilage and other surrounding tissues. In the end, this causes inflammation and pain. (8)

But subchondral sclerosis is not the only problem.

As knee osteoarthritis progresses, the subchondral bone goes through even more changes that cause (4, 9):

Knee Force Knee Sleeve
  • Bone spurs, also known as osteophytes.
  • Bone marrow lesions (BML) – their presence is directly related to symptomatic knee osteoarthritis.
  • Subchondral cysts – a hallmark of advanced OA.

3) Synovium

This is the combination of two structures (4):

  • The synovial membrane – a tissue that surrounds the inner surface of the joint capsule.
  • The synovial fluid – a liquid secreted by the synovial membrane.

This intra-articular fluid is full of nutrients, hyaluronic acid, and other lubricants. So, apart from allowing smooth movement, it also keeps the chondrocytes nurtured. (4)

Now, the membrane shows signs of inflammation even in the early stages of knee osteoarthritis. This is known as “synovitis” and can happen well before the wear and tear begin. (10)

Synovitis is associated with the severity of symptoms and the progression of knee OA.

This is partly because it induces an immune system response, which irritates the tissues via chemicals that cause pain and swelling.

If that wasn’t enough, synovitis also triggers the production of enzymes that damage the cartilage. This in turn creates molecules that propagate the inflammation to other parts of the joint.

The relationship between osteoarthritis and synovitis is so strong, that the areas of irritated membrane can relate to those of cartilage degradation. (4)

4) Infrapatellar pad

This is an adipose structure also known as “Hoffa’s infrapatellar fat pad” (IPFP). It’s at the front of the knee, behind the patellar tendon – right between the synovium and the capsule. It works as a shock absorber, protecting the knee from damage.

It’s a very sensitive tissue as well. It contains a variety of cells that interact with the immune system. Also, it can release substance P – a chemical associated with pain. (4)

Knee osteoarthritis patients tend to have high levels of this substance in their synovium, which in turn causes local swelling and can worsen cartilage degradation. (11)

In the long term, this can alter the structure of IPFP. Researchers believe these changes in Hoffa’s fat pad are big contributors to the chronic knee pain associated with osteoarthritis. (4)

5) Menisci

A meniscus is a C-shaped cartilage that also works as a shock absorber. We have two on each knee – the medial and lateral menisci.

Now, a meniscus tear is a strong risk factor for developing knee osteoarthritis. This is because this injury (4):

  • Can change your knee joint mechanics, loading one area more than the other.
  • May cause joint instability, which also changes the distribution of the mechanical load in the joint.
  • Will trigger an inflammatory response to heal the tissue, which can lead to synovitis and bone marrow lesions.

Another issue is that patients with radiographic evidence of osteoarthritis tend to have some level of meniscus damage. This shows that the wear and tear process itself can tear this structure.

This means that meniscus injuries can cause osteoarthritis and vice versa. (4)

Related: What happens if a meniscus tear goes untreated?

6) Muscles and tendons

Knee osteoarthritis usually has some sort of muscle weakness associated with it. Mostly in the quadriceps, hamstrings, and hip muscles. This weakness significantly alters the biomechanics of the affected joints, making them prone to deterioration.

Also, studies show that the muscles surrounding an osteoarthritic knee joint are inflamed and can produce myokines. These are chemicals that can have a pro-inflammatory effect which affects the synovium, IPFP, cartilage, and subchondral bone.

However, strengthening these muscles can reduce the secretion of myokines, helping with symptoms and overall joint inflammation. It can also delay the need for knee joint replacement. (4)

This can help: 6 home exercises to strengthen your knee joints.

7) Ligaments

These are strong bands of tissue that help keep the joint stable. We have many of them in each knee, but the ones that tend to get injured are the cruciate and collateral ligaments.

Around 50% of people with ligament injuries end up developing knee osteoarthritis after 10-20 years. (4) The reasons are similar to those of meniscus tears – changes in joint mechanics and the innate inflammatory response.

However, patients with torn ligaments can decrease their risk of osteoarthritis with proper treatment. (4)

Related: How to heal a knee sprain fast?

The role of low-grade inflammation in knee osteoarthritis

Inflammation is a natural response of the immune system. There are two types – acute and chronic (or low-grade).

Think about the last time you sprained your ankle. It got swollen, right? Well, this is acute inflammation in action. Here, your immune system is flooding the area with cells that repair the injured tissue.

These cells also cause varying degrees of pain. This is to remind you that the area is vulnerable, so you don’t make the injury worse.

It quickly gets better, though. As the tissue heals, the immune response calms down because you don’t need it anymore.

Chronic inflammation isn’t that obvious, though.

The trigger is the same – your immune system wants to get rid of something it perceives as a threat. But the danger has to do more with lifestyle issues or medical conditions, rather than a specific injury.

Here, the inflammation isn’t in one specific place, but through the entire body. It silently wreaks havoc on our joints and organs.

The following are examples that can cause and maintain chronic inflammation (12):

  • Smoking.
  • Drinking alcohol.
  • Not doing physical activity.
  • Stress.
  • Excess weight/obesity.

But, what does this have to do with knee osteoarthritis?

Well, it turns out that the immune system is heavily involved in joint health as well, as it dictates (4):

  • The rate at which the chondrocytes and ECM work to rebuild cartilage.
  • How bones – like the subchondral bone – remodel themselves.
  • The presence (or lack thereof) of the typical knee OA symptoms – pain, swelling, and stiffness.

An altered immune system will inevitably affect the way your knee works on a chemical level.

For example, it can make it harder for you to heal from a meniscus tear or synovitis. Thus keeping these injuries for longer and setting the stage for cartilage degradation.

This is also one of the reasons why obesity increases the risk of OA.

Apart from the excess weight on the knees, the low-grade inflammation associated with obesity can damage the cartilage.

Researchers believe this is why these patients are prone to hand, hip, and knee osteoarthritis, among other joint problems. (13)

This might help: The ideal supplement for strengthening your immune system – Immune Complex.

Risk factors for knee osteoarthritis

Apart from obesity, advanced age increases the likelihood of developing knee osteoarthritis. And as you learned above, previous knee injuries like meniscus or ligament tears also make the joint prone to degeneration.

However, another risk factor is overuse – whether from professional sports activities or physical jobs. This is mostly because they make the joint prone to injuries.

Sedentarism contributes to not only knee but hip joint osteoarthritis as well, as it weakens the muscles and doesn’t stimulate cartilage growth.

Other factors include (4):

  • Being a female – wider hips and narrower femurs increase the risk of developing OA.
  • Genetic predisposition.
  • Ethnic group – African Americans tend to have higher rates of knee OA.

Treatment options for knee joint osteoarthritis

To date, there’s no therapy capable of reversing cartilage degradation to pre-injury levels. Current treatments focus on providing knee pain relief and preventing the condition from getting worse. (10)

There are several ways to do this, though. The treatment plan will depend on the symptoms, stage of the condition, lifestyle, overall health, and preferences of the patient.

With that said, there are common denominators in all treatments for knee OA.

Take exercise, for example. After looking at the pathophysiology of the disease, it makes sense to have it as a staple in wear and tear treatment.

See, apart from keeping muscles strong, it also promotes cartilage health. It’s extremely effective for managing low-grade inflammation as well. (4)

The best part is that it doesn’t have to be anything fancy. Strength training is ideal, but so are walking, tai chi, and yoga. The type of exercise you do is not as relevant as your ability to stick to it. (14)

Learn more: Best treatments for knee OA according to evidence.

Weight loss is another effective treatment for a reason.

It reduces the load on the affected joint and keeps chronic inflammation at bay – two factors that definitely slow down knee OA’s progression.

For people with a BMI >25, losing 5 to 10% of body weight can be enough to provide benefits. And the recommended way to do this is with a combination of exercise and dietary changes. (14)

Other conservative treatments for knee OA include:

Yet, some people will need surgery.

Their joint stiffness or chronic pain may be so severe it limits their daily lives. In this scenario, having a partial or total knee replacement is the right choice.

However, there are a lot of gray areas here. And the consequences of having knee surgery if you don’t really need it can be devastating. It can even worsen the pain and physical limitations. (14)

That’s why we made a guide to help you know whether you need knee surgery or not. It gives you facts and questions to ask yourself so you can make the best decision.


How does osteoarthritis occur in the knee?

Aging, overuse of knee joints, sedentarism, chronic inflammation, and risk factors like rheumatoid arthritis or obesity.

What are the stages of knee osteoarthritis?

Doubtful, mild, moderate, and severe.

What happens in osteoarthritis of the knee joint?

The articular cartilage wears off while other structures of the knee get inflamed and painful. This can severely limit the quality of life of the patient to the point of needing a knee replacement.

Conclusion: Pathophysiology of osteoarthritis of the knee

The pathophysiology of this condition is very complex, with several structures affected – not only the cartilage.

Even though the combination of risk factors can really increase the risk, certain lifestyle choices can counteract the damage.

This means that you have more control over knee osteoarthritis than you may think. So, if you need more tips, make sure to check this guide on how to live with knee OA.


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  2. Hsu H, Siwiec RM. Knee Osteoarthritis. [Updated 2022 Apr 30]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from:
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  8. Roemer, F W et al. “Subchondral bone marrow lesions are highly associated with, and predict subchondral bone attrition longitudinally: the MOST study.” Osteoarthritis and cartilage vol. 18,1 (2010): 47-53. DOI: 10.1016/j.joca.2009.08.018
  9. Donell, Simon. “Subchondral bone remodelling in osteoarthritis.” EFORT open reviews vol. 4,6 221-229. 3 Jun. 2019, DOI: 10.1302/2058-5241.4.180102
  10. Sokolove, Jeremy, and Christin M Lepus. “Role of inflammation in the pathogenesis of osteoarthritis: latest findings and interpretations.” Therapeutic advances in musculoskeletal disease vol. 5,2 (2013): 77-94. DOI: 10.1177/1759720X12467868
  11. Paduszyński, Wojciech et al. “Hoffa’s Fat Pad Abnormality in the Development of Knee Osteoarthritis.” Advances in experimental medicine and biology vol. 1039 (2018): 95-102. DOI: 10.1007/5584_2017_77
  12. Watson, S. “All about inflammation.” [June 15, 2020]. Harvard Health. Retrieved on May 2022 from:
  13. Robinson, William H et al. “Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis.” Nature reviews. Rheumatology vol. 12,10 (2016): 580-92. DOI: 10.1038/nrrheum.2016.136
  14. American Academy of Orthopaedic Surgeons Management of Osteoarthritis of the Knee (Non-Arthroplasty) Evidence-Based Clinical Practice Guideline (3rd Edition). Published on August 31, 2021.
Mitch Torres (PT)
Mitch is a physical therapist, personal trainer, and nutrition coach. Fascinated with the knee joint, Mitch poured that passion into writing about knee pain and how to overcome it with movement. His goal is to teach you how to apply this knowledge into your daily life, so you can keep knee pain away for good.