A Scientific Editorial - Articular Cartilage Regeneration

The Regeneration of Articular Cartilage with Prolotherapy

Cartilage"> Author: Ross A. Hauser MD

Simply put, I believe that articular cartilage is regenerated with Prolotherapy. In my opinion, Prolotherapy should be the treatment of choice for most cases of pain involving the degeneration of a joint. It is common knowledge that even the most effective current treatments for osteoarthritis do not restore the joint. Conservative treatments such as exercise, medications, physical therapy, and lifestyle modification can decrease symptoms and improve mobility, but they do not reverse the disease. I believe if Prolotherapy were utilized to its fullest in the treatment of knee, shoulder, and other peripheral joint degenerative conditions, it would be shown to be the one treatment that does restore some, or most, of the degenerated structures, as well as the functions of the joint.

What most people may not realize is that chondrocytes, the cells that make articular cartilage, are metabolically active.^[1] Yes, chondrocytes do proliferate and actively make articular cartilage. In normal cartilage, there is a strict regulation of cartilage turnover, a delicate balance between synthesis and degradation. The problem is, for those suffering from osteoarthritis, the system is imbalanced. There is more cartilage degeneration than rebuilding.

In osteoarthritis, both degradation and synthesis of articular cartilage are enhanced. The problem is that the “messenger” molecules that allow cells to communicate and alter one another’s functions, called cytokines, cause more breakdown of articular cartilage than repair. The catabolic (break down) cytokines IL-1, TNF-a, IL-17, and IL-18 act to decrease extracellular matrix synthesis (cartilage synthesis). The anabolic cytokines (substances that build up) IGF-1, TGF-B1, 2, and 3, fibroblast growth factors (FGFs) 2, 4, and 8, and the bone morphogenetic proteins act to stimulate extracellular matrix synthesis.^[2,3] In osteoarthritis, unfortunately, the catabolic cytokines are winning.

It is well known that in osteoarthritis, chondrocytes retain their proliferative activity.^[4,5,6] As a matter of fact, a number of biochemical studies have demonstrated enhanced synthesis of the extracellular matrix of cartilage.^[7,8] Chondrocytes attempt to repair the damaged matrix in osteoarthritis by increasing their anabolic activity.^[9,10] One of the reasons for this is that on a molecular level, a significant proportion of adult articular chondrocytes start to re-express a chonodroprogenitor phenotype in osteoarthritic cartilage degeneration, which is comparable to the chondroprogenitor phenotype observed in fetal skeletal development.^[11,12] In other words, with injury/ degeneration, the adult chondrocyte cells change to more “primitive” cells, which have more proliferative ability. In the natural history of the disease, despite this increased activity, a net loss of proteoglycan content (extracellular cartilage matrix) is one of the common features of all stages of osteoarthritic cartilage degeneration.^[13]



One of the main hallmarks of osteoarthritis in a joint is the development of prominent osteochondral nodules known as osteophytes. These are also called osteochondrophytes or chondroosteophytes. Most of us know them as bone spurs. Indeed, the presence of osteophytes in a joint, more than any other pathological feature, distinguishes osteoarthritis from other arthritides.^[14] Osteophytes are an example of new cartilage and bone development in osteoarthritc joints, and arise from tissue associated with the chondro-synovial junction or from progenitor cells residing in the perichondrium.^[15,16] This basically means there is a population of joint cells (pluripotential cells) that can respond to injury and differentiate into cells that make cartilage and bone. The purpose of osteophytes is presumed to be the stabilization of joints affected by osteoarthritis.^[17]

When larger osteophytes are examined from human patients, areas of hyaline cartilage can be seen to extend to the surface of the osteophyte. These cartilaginous tissues resemble genuine articular cartilage in chondrocyte morphology and in extracellular matrix. Interestingly, the anabolic factors TGF-B and TGF-B2 have been found in osteophytes from human femoral heads.^[18] Again this signifies that adult articular cartilage retains repair (anabolic) activity.