Hormone and Growth Factor involvement in Cartilage Regeneration

Prolotherapy and Hormones

Prolotherapy is a specialized medical procedure and technique that permanently and non-surgically eliminates chronic pain that results from joint instability caused by ligament laxity. When an injury occurs, cells break open and release basically fat and sugar. This creates an inflammatory reaction that triggers the body’s immune system to release growth factors. Unfortunately, blood flow to ligaments and tendons is normally weak. This situation is exacerbated by taking anti-inflammatories such as aspirin and ibuprofen or stronger prescription NSAIDs.

Whenever it comes to cartilage loss, anabolic hormones such as testosterone play a role in regenerating it. Research shows that estrogen receptors are present in cartilage and that estrogen stimulates cartilage growth.1

Similarly testosterone has been shown to have a direct effect on cartilage growth. Testosterone, for example, is an anabolic hormone (i.e. synthesized into living tissue). Anabolic hormones, which are responsible for protein synthesis, enhance production of muscle and cartilage growth. Many people believe that testosterone is only a male hormone, but it actually plays a pivotal role in the female body chemistry as well. If one has a low testosterone level, then they will likely experience more difficulty healing.

Testosterone is made by men in the testicles, and females the ovaries. There is also a small production that is created in the adrenal glands. Although the adrenal gland is able to produce a small amount of testosterone, many patients of both genders suffer from depleted adrenals as a result of stress. This stress can arise from pain, lack of sleep, and a myriad of personal issues. So sometimes treating adrenal fatigue to optimize hormone production is called for.

Proliferation, Hormones, and Growth Factors Promote Cartilage Regeneration

A Swedish study recently focused on the effects of testosterone on chondrocytes to determine whether testosterone was dependent on the stage of maturation or was gender specific. The research concluded that testosterone promotes differentiation of chondrocytes (cartilage cells) and increases collagen production. It was dependent on time of exposure, presence of serum, gender, and stage in chondrocyte maturation. It also mentions that age, height and weight are associated with sex steroid levels.2

In another study, researchers examined whether testosterone supplementation could help prevent total knee replacement. They looked at various factors that can affect knee cartilage volume. Earlier studies had shown that tibial cartilage volume in healthy men decreased 2.8% per year. They were particularly interested in measuring serum testosterone levels and total bone mineral content. They hypothesized that hormonal manipulation and/or treatment with bone antiresorptive drugs could reduce cartilage loss/osteoarthritis in men. They found that, “serum testosterone level at baseline and urinary NTx, a marker of bone turnover were inversely related to cartilage loss.”3

So again, it seems like there may be a correlation between optimal testosterone levels and healthy cartilage.

In one landmark study, doctors showed how androgens (anabolic hormones) reversed cartilage damage and reduced proteoglycan loss. Women are two to three more times more common and more likely to have the disease become more disabling and aggressive than men. It suggests that a long-term androgen replacement may help prevent joint damage and disability.4

Testosterone can help improve cartilage health and making sure your hormonal levels are optimal is pivotal to stable healthy joints. This new knowledge is key to the future diagnosis of degenerative diseases; it will help keep patients unnecessarily off the operating table and allow them to improve on their quality of life without painful recovery times. In addition to these facts, avoiding degenerative treatments such as NSAIDs and steroid injections, and choosing regenerative treatments such as Prolotherapy will allow patients to regenerate their cartilage and avoid joint replacement surgery.

The Role of Melatonin

Doctors at Sun Yat-sen University in China recently published research in the journal Advances in free radical biology and medicine in which they suggested melatonin could alter the disease joint environment of the knee.

Cartilage repair by mesenchymal stem cells (MSCs) often occurs in diseased joints in which the inflamed microenvironment impairs chondrogenic maturation (prevents cartilage growth) and causes neocartilage degradation (the diseased environment of the knee does not allow new cartilage to develop.

In this environment, melatonin exerts an antioxidant effect by scavenging free radicals. The results of introducing melatonin into the diseased knee environment demonstrated that proinflammatory cytokines impair the chondrogenesis of MSCs (inflammation destroying cartilage), was reversed by melatonin treatment. Melatonin provides a new strategy for promoting cell-based cartilage regeneration in diseased or injured joints.5

1. Engdahl C, Börjesson AE, Forsman HF, Andersson A, Stubelius A, Krust A, Chambon P, Islander U, Ohlsson C, Carlsten H, Lagerquist MK.  The role of total and cartilage-specific estrogen receptor alpha expression for the ameliorating effect of estrogen treatment on arthritis. Arthritis Res Ther. 2014 Jul 15;16(4): [Pubmed] [Google]

2. Lorentzon M, Swanson C, Andersson N, Mellström D, Ohlsson C. Free testosterone is a positive, whereas free estradiol is a negative, predictor of cortical bone size in young Swedish men: the GOOD study. Journal of Bone and Mineral Research. 2005 Aug 1;20(8):1334-41. [Pubmed] [Google]

3. Hanna F, Ebeling PR, Wang Y, O’Sullivan R, Davis S, Wluka AE, Cicuttini FM. Factors influencing longitudinal change in knee cartilage volume measured from magnetic resonance imaging in healthy men. Ann Rheum Dis. 2005 Jul;64(7):1038-42. Epub 2005 Jan 7. [Pubmed] [Google]

4. Da Silva JA, Larbre JP, Spector TD, Perry LA, Scott DL, Willoughby DA. Protective effect of androgens against inflammation induced cartilage degradation in male rodents. Ann Rheum Dis. 1993 Apr;52(4):285-91. [Pubmed] [Google]

Liu X, Xu Y, Chen S, Tan Z, Xiong K, Li Y, Ye Y, Luo ZP, He F, Gong Y. Rescue of proinflammatory cytokine-inhibited chondrogenesis by the antiarthritic effect of melatonin in synovium mesenchymal stem cells via suppression of reactive oxygen species and matrix metalloproteinases. Free Radical Biology and Medicine. 2014 Mar 31;68:234-46. [Pubmed] [Google]