Photomicrographs of histological sections of various sample cartilages have previously been stained by Alcian blue or with specific antibodies against proteoglycans (decorin, biglycan, and aggrecan), chondroitin (chondroitin-6-sulfate, chondroitin-0-sulfate, and chondroitin-4-sulfate) and keratan sulfate, or type I and II collagen. Researchers have also used the SAM (Significance Analysis of Microarrays) technique to mark the chondrocytes sample with low chondrogenic capacity. These samples displayed higher levels of catabolic genes (aggrecanase 2, matrix metalloproteinase 2, etc.) and insulin-like growth factor 1. High chondrogenic capacity holding chondrocytes displayed high levels of cell-matrix or cell-cell contacting genes (CD49f, CD49c, etc.). According to flow cytometry analysis, CD44, CD49c, and CD151 showed significant distribution in higher chondrogenic capacity holding chondrocytes. The analysis further indicated that CD151 and CD44 hold the capability to detect more chondrogenic clones. Chondrocytes put under brighter CD49c or CD44 signal expression yielded tissues with higher amounts of GAG/ DNA (1.4-fold max) and type II collagen mRNA (3.4-fold max) than did non-brightened cells.[5]

As mentioned earlier, chondrocytes maintain homeostasis between the creation and destruction of extracellular matrix components. Chondrocytes, influenced by external stimuli, polypeptide growth factors, and cytokines, create such components and the enzymes which break them down.[6] A disruption in the homeostasis leads to osteoarthritis. Researchers are still unsure of the initial point of degradation. A microfracture from any trauma may cause the production of enzymes, leading to “wear” particle synthesis and its macrophage-caused destruction. Eventually, “wear” particle production inhibits systematic degradation of such particles, mediating inflammation and influencing chondrocytes to secrete degradative enzymes. Collagen and proteoglycan metabolism yield particles that cause proinflammatory cytokine releases, like TNF-alpha, IL-6, and IL-1. These cytokines can attach to chondrocyte receptors, which releases metalloproteinases and promotes inhibition of type II collagen assembly, thus proliferating cartilage degradation. Homeostatic disruption increases the water content and decreases the proteoglycan content of the extracellular matrix (ECM). This modification weakens the collagen network due to a drop in type II collagen synthesis and increases the breakdown of pre-existing collagen. Chondral apoptosis is also visible.

An increased anabolic and catabolic activity mark a patient with osteoarthritic cartilage. Compensatory mechanisms such as increased production of matrix molecules (collagen, hyaluronate, and proteoglycans) and the spread of chondrocytes in deep chondral layers manage the integrity of the articular cartilage. Chondrocyte loss, however, along with transformations in extracellular matrix predominates, causing osteoarthritic conditions.

Thinning cartilage, degrading cartilage thickness, and fibrillation of superficial layers are all caused by the initial degradations. These changes get worst over time, and articular cartilage (AC) thins to complete destruction. This condition exposes the underlying subchondral bone plate and characterizes these changes as chondropathy.[7] Current investigations about the heterogeneity of cellular reaction patterns that characterize osteoarthritic cartilage degeneration highlighted apoptotic chondrocyte death and its underlying mechanisms.[8]

Chondrocyte regeneration has contributed to the development of reconstructive procedures. Direct defects on articular cartilage (AC) cause severe pain; such acute and chronic pain could only be minimized with long-term treatments just three decades ago. Those conditions can now be permanently eliminated using a surgical procedure called autologous chondrocyte implantation (ACI).

Initially performed on soccer players by Swedish orthopedic surgeons in the early 90s, ACI attained US FDA authorization on August 22, 1997. The common pre-operational scenario includes a cracked hole on the joining surface of the articular cartilage. These defects may appear in patients aged 60 to younger patients (median age 31.3). Usually performed at the distal end of the femur, ACI has been successfully performed for kneecap deficiencies as well as other joint issues. In general, ACI divides into two phases: cell regeneration and open procedure. The patient’s MRI procedure first confirms a surgery-worth defect. Chondrocyte sample is taken via an arthroscopic procedure. New chondrocytes are produced via the enzymatic treatment of the collected sample for three to four months. After the production of over a million cells, the orthopedic surgeon proceeds to the second phase, open procedure. After an incision, the cultured chondrocytes are injected underneath a sewn patch, leading to chondral adhesion to the patient’s cartilage for natural regeneration. A weight-bearing restriction for a maximum of 8 weeks is common after the procedure.[9][10]