Arthritis isn’t a single disease with a single cause. It’s an umbrella term for more than 100 conditions that affect the joints, and each type has its own triggers. Osteoarthritis, the most common form, stems from mechanical wear and metabolic changes in cartilage. Rheumatoid arthritis is driven by a misdirected immune system. Gout comes from a buildup of uric acid crystals. Together, osteoarthritis and rheumatoid arthritis account for the vast majority of cases, affecting roughly 12% and 4% of U.S. adults respectively.
Osteoarthritis: Cartilage Breakdown Over Time
Healthy cartilage constantly rebuilds itself, balancing the natural breakdown of old tissue with the creation of new tissue. In osteoarthritis, that balance tips toward destruction. Enzymes that digest cartilage proteins become overactive, chewing through the two main structural components of cartilage: collagen (the tough, fibrous scaffold) and aggrecan (the spongy molecule that absorbs shock). Once cartilage thins and roughens, bones start grinding closer together, causing pain, stiffness, and swelling.
Several things push the balance toward breakdown. Joint injuries are a major one. Mechanical destabilization of a joint, whether from a torn ligament, a fracture, or repetitive stress, directly ramps up the production of those destructive enzymes. About 25% of people who tear an ACL and have it surgically reconstructed show osteoarthritis symptoms within 10 years. By 15 years, that number climbs to roughly 50%.
Aging plays a role too, but not simply through “wear and tear.” As cartilage cells age, they become senescent, meaning they stop functioning normally and start releasing inflammatory signals. Oxidative stress, the cellular damage caused by unstable molecules, further accelerates the process. These internal changes explain why osteoarthritis isn’t just a disease of people who overuse their joints. It can develop in anyone whose cartilage biology shifts in the wrong direction.
How Excess Weight Fuels Joint Damage
Carrying extra weight increases the mechanical load on your knees, hips, and ankles, which accelerates cartilage wear. But the relationship between obesity and arthritis goes beyond physics. Fat tissue is metabolically active. It releases signaling molecules called adipokines that travel through the bloodstream and promote inflammation throughout the body, including inside joints that aren’t even bearing extra weight.
One of these molecules, leptin, is directly linked to increased knee cartilage loss and joint pain. Others, like resistin and visfatin, trigger inflammatory and tissue-destroying processes in cartilage. Abnormal dietary patterns high in fats and sugar compound the problem by pushing fat cells to produce even more of these inflammatory signals. This metabolic pathway helps explain why obesity increases the risk of arthritis in the hands, not just in weight-bearing joints.
Rheumatoid Arthritis: The Immune System Attacks
Rheumatoid arthritis has a fundamentally different cause. Instead of cartilage wearing down, the immune system mistakenly attacks the tissue lining the joints, creating chronic inflammation that gradually erodes cartilage and bone. The trigger for this immune misfiring involves a combination of genetics and environment.
Genetics accounts for an estimated 44% of rheumatoid arthritis risk. The strongest known genetic link involves a set of immune system genes called HLA-DRB1. People who carry specific variants of these genes produce immune cells that are more likely to mistake the body’s own joint proteins for foreign invaders. But genes alone rarely cause the disease. Environmental triggers are needed to flip the switch.
Smoking is the single largest preventable risk factor. It’s responsible for an estimated 35% of cases involving a specific type of immune antibody (called ACPA) that attacks joint tissue. The risk increases with the amount smoked and interacts powerfully with genetic susceptibility. In people who carry two copies of the high-risk HLA-DRB1 gene variant, smoking accounts for 55% of their ACPA-positive rheumatoid arthritis risk. Other environmental triggers under investigation include certain infections, air pollution, and changes in gut bacteria, though none have as strong an evidence base as smoking.
Gout: Crystals in the Joint
Gout is caused by the accumulation of uric acid crystals inside a joint, most often the big toe. Uric acid is a normal waste product your body creates when it breaks down purines, compounds found in many foods and in your own cells. Problems start when uric acid levels in the blood rise above 6.8 mg/dL, the point at which uric acid can no longer stay dissolved and begins forming needle-shaped crystals.
These crystals settle into joint tissue and trigger an intense inflammatory response. The result is sudden, severe pain, redness, and swelling that often strikes overnight. Dietary drivers of high uric acid include alcohol (especially beer, which is rich in purines), organ meats like liver and sweetbreads, and high-protein diets. Your kidneys also play a role: most people with gout under-excrete uric acid rather than overproducing it, meaning their kidneys don’t clear it efficiently enough.
Psoriatic Arthritis: Skin Disease Reaches the Joints
Up to one-third of people with psoriasis eventually develop psoriatic arthritis, a condition where the same immune dysfunction that causes scaly skin patches also inflames the joints. In about 70% of cases, skin symptoms appear first, sometimes years before joint problems begin. In one study tracking psoriasis patients over three years, nearly 15% developed new joint inflammation.
Psoriatic arthritis can affect any joint but commonly targets the fingers, toes, lower back, and the spots where tendons attach to bone. The inflammation is driven by overactive immune signaling, particularly involving a group of inflammatory proteins that overlap with those seen in psoriasis. Having nail psoriasis (pitting, discoloration, or separation of the nail) is a particularly strong predictor of developing joint involvement later.
Infectious Arthritis: Bacteria in the Joint
Unlike the other forms, septic arthritis is caused by bacteria that enter a joint directly, usually through the bloodstream from an infection elsewhere in the body, or through a wound or surgery. Staphylococcus aureus is the most common culprit, followed by Streptococcus species. In older adults, gut-related bacteria like E. coli cause 23% to 30% of cases. In sexually active young adults, gonorrhea is an important cause to consider.
Septic arthritis is a medical emergency. The bacteria rapidly destroy cartilage, and without prompt treatment, permanent joint damage can occur within days. It typically affects a single joint, most often the knee, and comes on suddenly with severe pain, swelling, warmth, and fever.
The Role of Genetics Across All Types
Genes don’t cause arthritis on their own, but they set the stage. Osteoarthritis has a heritability of about 51%, meaning roughly half of the variation in who develops it can be traced to inherited factors. Rheumatoid arthritis is similar at around 44%. A related condition, psoriatic arthritis combined with spinal inflammatory arthritis, has the highest heritability at approximately 64%.
What’s inherited isn’t arthritis itself but rather traits that increase vulnerability: the shape and alignment of your joints, the resilience of your cartilage, how aggressively your immune system responds to triggers, or how efficiently your kidneys clear uric acid. These genetic predispositions interact with life events like injuries, infections, weight gain, or smoking to determine whether arthritis actually develops. That interaction is why two people with the same genetic risk can have very different outcomes depending on their exposures over a lifetime.