Bone morphogenetic proteins (BMP’s) are a family of soluble cytokines (signaling factors) which play a prominent role in the development, growth, maintenance and repair of bone and cartilage tissues. Originally identified in the mid 1960’s, BMP’s have been successfully employed by orthopedic surgeons to assist in the re-growth of bone tissue, post surgery, since the late 1980’s. Additionally, BMP’s are structurally robust and survive, intact, the acidic environment within the stomach, thereby allowing these proteins to be used as an orally administered nutritional supplement in support of a joint and bone healthy lifestyle.
To truly grasp the power of BMP’s it is first necessary to understand their history. Dr. Marshall Urist, an orthopedic surgeon and head of the Bone Research Center at UCLA began with a simple question, “What makes bone re-grow after injury?” During the course of his research, Dr. Urist extracted a protein from bones which had the ability to transform mesenchymal stem cells (MSC) into cartilage and bone matrix synthesizing cells known as chondrocytes and osteoblasts. This “osteoinductive” ability would become the distinguishing feature for all BMP’s.
Modern molecular biologists built upon this foundation and identified approximately 20 additional proteins with osteoinductive properties. Over 11,000 peer reviewed articles have been published on BMP’s and their mechanism of action. Both in vivo and in vitro BMP’s work by binding to extra-cellular receptors which initiates a signaling cascade resulting in the expression of genes specific to osteoblast and chondrocytes, thereby promoting the differentiation of MSC’s into mature, matrix secreting cells.
The implications of this protein’s signaling powers are profound. It is generally accepted that numerous chronic bone and joint conditions are a result of decreased matrix synthesis. Chief among these conditions is osteoporosis which is the result of an imbalance between osteoblast and osteoclast activity (bone degrading cells). After menopause, estrogen levels decrease in women. Estrogen is also a key regulator of osteoblast activity. A reduction in estrogen signaling, hinders the deposition of de-novo bone material and results in a net weakening of the tissue. BMP’s may therefore be used to replenish the pool of activated osteoblasts. These activated osteoblasts synthesize a collagen platform upon which calcium and other necessary minerals bind in order to strengthen bone tissue.
The synergistic response between mineral supplementation and osteoblast activation is not surprising. Mineral supplementation has limitations in restoring bone mineralization if the mechanism of utilization (osteoblast activity) is down regulated. The synergistic impact of both BMP and mineral supplementation was presented in a case study on a postmenopausal woman with 53 months of documented bone loss. When given a BMP complex as a nutritional supplement, in conjunction with her normal calcium/vitamin D regiment, the subjected stabilized her bone mineral loss in 8 months then proceeded to see a recovery of 51.5% of her bone density over a subsequent period of 34 months (Tripodi 2013).*
BMP’s also promote the differentiation of MSC’s into chondrocytes which are key to synthesizing the long protein chains found with cartilage tissue. These chains possess remarkable elastic properties, which when coupled with their ability to retain water, serve to stabilize and lubricate joints. This claim is supported by clinical evidence that demonstrated BMP-6 is key to maintaining joint integrity. Additionally decreased levels of BMP-4 and BMP-5 were observed in the synovial membrane of individuals suffering from knee pain further supporting the claim that BMP’s provide a central role in maintaining the structural integrity of articular cartilage.
In addition to BMP’s impact on bone and cartilage synthesis, preclinical evidence has demonstrated that BMP’s have an immunoprotective effect. Specifically BMP’s are known to down regulate interleukins -1 and -6, which are key signaling molecules in the inflammation response pathway. Specifically, IL-1 activates and matrix metalloproteinases which are known to destroy cartilage (Bobacz et al., 2003, Bramlage et al., 2006).
Based upon these results, it seems clear that there is a connection between a reduction in BMP signaling activity and the progression of degenerative joint disease. Therefore supplementation of the diet with BMP’s would have a beneficial effect on overall joint health and inflammation response. This was proven true during a small case study in which an all-natural BMP complex was administered individuals with degenerative joint disease. At the conclusion of the 6 month study, subjects reported a 40% increase in all quality of life markers and a decrease in inflammation and pain (Garian and Scaffidi 2013).
The usage of BMP’s as a bone and joint supplement is in its infancy, yet it is supported by nearly 40 years of academic research and nearly 25 years of surgical usage. Supplements containing a BMP complex are available through ZyCal Bioceuticals.
Written by: Matthew Walker Ph.D. Senior Clinical Trials Manager ZyCal Bioceuticals
Sources:Bramlage C.P., Häupl T., Kaps, C., Ungethüm U., Krenn V., Pruss A., Müller G.A. , Strutz and Burmester G. Decrease in expression of bone morphogenetic proteins 4 and 5 in synovial tissue of patients with osteoarthritis and rheumatoid arthritis. Arthritis Res Ther 2006;8(R58). Bobacz Z., Gruber R., Soleiman A., Erlacher L., Smolen S., and Graninger W.B. Expression of Bone Morphogenetic Protein 6 in Healthy and Osteoarthritic Human Articular Chondrocytes and Stimulation of Matrix Synthesis In Vitro. Arthrits Rheumatol 2003; 45(9): 2501-2508 Garian R., Scaffidi J. Evaluating Clinical Response and Activity of Cyplexinol Osteoinductive Proteins in Osteoarthritis of the Hip and Knee: A Randomized, Controlled Trial. IMCJ 2013; 12(2):18-24. Tripodi D. The Osteoinductive Effects of Cyplexinol in the Effective Management of Osteoporosis: A Case Study. IMCJ 2013;12(5):43-46.
*These statements have not been evaluated by the Food and Drug administration. These products are not intended to diagnose, treat, cure or prevent any disease.
**This blog was written by an outside source. This blog does not necessarily reflect the views or positions of Natural Partners.