Osteoinductive Protein Complex: Growing de novo bone and cartilage tissue via stem cell activation

October 31, 2018

Clinical Rounds Educational Series: Growing de novo bone & cartilage tissue

The term osteoinduction refers to the differentiation of stem cell (SC) progenitors into osteoblasts and chondrocytes. This process is regulated by a group of proteins in the transforming growth factor-ß (TGF-ß) superfamily knowns as bone morphogenetic proteins (BMPs). Specifically, this signaling pathway propagates bone and cartilage matrix synthesis (tissue) through osteoblast and chondrocyte differentiation, which subsequently promotes de novo bone growth and cartilage formation. The term “osteoinduction” was first coined by the orthopedic surgeon Dr. Marshall Urist in his seminal work The Autoinduction of Bone, published in 1965 in the journal; Science.  Osteoinduction coined by Dr Urist in 1965

Dr. Urist was head of bone research at UCLA, on a quest to understand exactly what in bone caused it to heal post-fracture. Urist developed a technique to remove all of the mineral and cellular components within bone, leaving behind the collagen framework with a newly discovered bound protein. When this complex was presented to mesenchymal stem cells, Urist noted that the new protein complex induced stem cells to morph or differentiate into osteoblasts and chondrocytes producing de novo bone and cartilage tissue. He called this new protein Bone Morphogenetic Protein and published his findings in 1965, ushering in a new field of research and clinical medicine, which today is known as osteobiologics.

As cell and molecular biology techniques improved in the 1970s and 1980s we came to learn that Urists’ discovery was not a singular bone morphogenetic protein attached to a collagen molecule, but in fact was an entire family of BMPs covalently bound to and embedded within the collagen molecule. To date, we have discovered that there are 22 isoforms of BMPs within the body with BMP-2 through BMP-10 concentrated within the bone matrix or tissue.

Cyplexinol(R) is the only ingredient proven to grow de novo bone tissueIn the 1980’s as orthopedic surgeons began seeking alternatives to autograft for spinal fusions, a team of researchers and business executives realized the first medical use for Urists’ collagen-BMP-complex. By extracting this complex from human donor bones, scientists and surgeons were able to bring forth the first osteoinductive BMP-complex as an alternative to harvesting autograft.

The BMPs within this topically applied BMP-complex promote osteoinduction by acting upon transmembrane serine/threonine kinase receptors. In their downstream signaling, BMPs bind to either type 1 or 2 receptors for the activation of specific intracellular messengers known as SMADs. Osteoinduction primarily utilizes activation of SMADs 1, 5 and 8 for downstream signaling. More specifically, BMP-activated type I receptors phosphorylates the intracellular signaling proteins SMAD1, 5, and 8, thereby forming heteromeric complexes with the common mediator SMAD, SMAD-4. The activated complex subsequently translocates to the nucleus and acts as a transcription factor inducing the expression of BMP-responsive genes. Thus, the activation of SMAD complexes induces mesenchymal stem cell (MSC) DNA, which propagates the differentiation of MSCs into either osteoblasts or chondrocytes. By leveraging the same extraction techniques, this BMP-complex is extracted from a certified organic, ultra-premium, food-source yielding the only osteoinductive complex for natural bone and joint health; known as Cyplexinol®. Cyplexinol® is a patented ingredient, manufactured in a cGMP, FDA registered facility managed by some of the same scientific and management experts from the pioneering surgical company, partnered with top executives from fortune 500 companies. And what makes Cyplexinol® so different is that it is the only ingredient proven to grow de novo bone tissue, providing the critical surface for minerals to bind to for healthy bones.* In joints, Cyplexinol® is the only ingredient proven to turn MSCs into chondrocytes for new cartilage tissue growth via proteoglycan excretion.*

Calcium and calcium complexes with vitamin D3 supplementation have been the mainstay of bone supplements for years, providing the fortification of bone tissue. Other dietary supplements have offered healthcare professionals alternative options, but none with the specific function and activity that is unique to a BMP-complex. Milk basic protein (MBP) is an isolate of whey that has been used to help support bone health in menopausal women.* Current clinical evidence supports that MBP’s may work through mediation of osteoclastic bone resorption.* This has its limitations on effectiveness, with no osteoinductive capability. Another compound, known as Protomorphogens (PMG) “is a brand name applied to these uniquely derived extract.”* However, PMGs as described by the manufacturer refers to a the mineral backbone of DNA which is a phospho-di-ester backbone for nucleic acids. To date there has been little clinical efficacy shown with PMB’s which in fact are not osteoinductive.

Cyplexinol® is a biologically active BMP-collagen complex, which confers it’s osteoinductive activity upon binding to receptors within the GI mucosa.* The tertiary and quaternary conformation of the BMP-collagen-complex (BMP-complex) resists enzymatic and hydrolytic degradation. Furthermore, bioavailability studies have demonstrated that BMP absorption can be attributed to the presence of specific BMP receptors in the stomach and ileum of animals, which transport the active BMP peptide, further aiding in preventing its hydrolysis into amino acids.

In a recent clinical trial, participants who took 150 mg of Cyplexinol® daily for 12 weeks reported a significant decrease in occasional pain and stiffness along with a heightened quality of life in comparison to the controls. The statistically significant onset of action occurred by day seven offering a novel approach to joint health. Clinical Trial Results as fast as 7 Days

BMPs have been shown to be an integral part of good bone health as they provide the biochemical signal necessary to activate the mesenchymal stem cells, transforming it into an osteoblast producing de novo bone tissue. This bone tissue provides the essential framework for calcium and other minerals to adhere to, yielding health bones. In recent studies of Cyplexinol®, coupled with calcium and vitamin D3, has been shown to be an integral component in providing the balance this is required for healthy bone and people with varied bone support needs*.

BMP-complex utilization for stimulation of Osteoinduction has an ever-growing focus in the research community, with implications in various areas of bone health, including a long history of research and utilization in the surgical field. Cyplexinol®, the only oral BMP-complex is providing healthcare practitioners with an unparalleled level of scientific evidence and clinical support, is ushering in a paradigm shift in the natural bone and joint market. Today, Cyplexinol® is manufactured by ZyCal Bioceuticals in an NSF-certified, cGMP, FDA registered facility and available in many healthcare and retail brands including Ostinol™ Advanced Bone and Cartilage Stimulating Proteins in several strengths to help healthcare practitioners meet a variety of bone and joint health needs.

“What makes Cyplexinol® so different is that it is the only ingredient proven to grow de novo bone tissue, providing the critical surface for minerals to bind to for healthy bones.”

William Franke, PhDDr. Franke has twenty-eight years of senior management experience at Unilever. He was Vice President for R&D, Quality and Regulatory Affairs at Unilever’s Lipton division. He then served as Vice President for Scientific and Regulatory Affairs, reporting to the President, CEO and Chairman, and was responsible for nutritional science for all of Unilever’s United State businesses. Dr. Franke founded Heart Blend Foods, LLC, a research and development company that specializes in the development of heart-healthy foods. Dr. Franke is Associate Director of the Center for Advanced Foods at Rutgers University and is an expert in the area of product development and food regulations, especially as it related to functional foods and nutraceuticals.




Osteoinductive protein complex: Growing de novo bone and cartilage tissue via stem cell activation

Part 1


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