Clinical Uses of Oral Osteoinductive Protein Complex: Meeting the unmet medical need in bone and cartilage management

October 31, 2018

Clinical Uses of Oral Osteoinductive Protein Complex: Meeting the unmet medical need in bone and cartilage management

While there are a number of dietary supplements on the market that support bone and cartilage health, there is still an unmet medical need in relation to products that stimulate the growth of new bone and cartilage tissue.* Supplements such as calcium, D3, and K2 help fortify tissue, which sustain or enhance its physiological state, but does not propagate new tissue growth. While these types of nutrients do provide some of the building blocks for bone and cartilage, how these nutrients are utilized, and what stimulates the growth and development of the tissue itself, is a critical question. The answer lies in the osteogenic and chondrogenic activity of cells known as mesenchymal stem cells (MSCs), which utilize the building blocks and cofactors as they grow de novo tissue.

BMB Signaling

Research now shows that the activation and differentiation of MSCs require a specific signaling cascade that is primarily regulated by osteoinductive proteins known as bone morphogenetic proteins (BMPs). Cyplexinol® is the only BMP-complex proven to differentiate MSCs into osteoblasts and chondrocytes- which grows de novo bone and cartilage tissue.*

Calcium, D3, and K2 work in conjunction to help fortify bone tissue. D3 promotes gastrointestinal calcium absorption through calcium influx; the translocation of calcium through enterocytes, and the basolateral extrusion of calcium by the intestinal plasma membrane pump.* K2 directs the transportation of calcium through the activation of osteocalcin; which is an important protein that is
secreted by osteoblasts.* Osteocalcin facilitates the binding of calcium into the matrix (tissue) of the bone. Additionally, the activation of osteocalcin by K2 also helps prevents calcium from being deposited in the coronary arteries.* Further, the combination of K2 and D3 provides some inhibitory effect on bone resorption by osteoclasts.* However, none of these processes stimulate the differentiation of MSCs into osteoblasts to produce de novo bone tissue.

Similarly, supplements such as glucosamine/chondroitin, MSM, and SAMe have
been traditionally recommended for people for support. Glucosamine is a sugar that is naturally produced in the body and is typically found in cartilage as well as other connective tissues.

Osteogenic and Chondrogenic Activity

Chondroitin is a carbohydrate that promotes water retention in cartilage which provides protective cushioning for various joints.* Supplementation with these two nutrients has shown conflicting data but in the GAIT study published in 2006, the
combination was shown to provide some symptomatic relief in a sub-cohort.* MSM also targets inflammatory signals and in some studies, has demonstrated free radical scavenging activity, properties that are believed to support the removal of metabolic waste that may lead to inflammation in the joints.* SAMe in some studies has shown some effect on inflammatory pathways as well and
elicits a mild analgesic effect in some people.* In clinical trials and practice,
glucosamine/chondroitin, MSM, and SAMe have demonstrated some clinical benefits.* They function primarily as building blocks which chondrocytes absorb to
create cartilage tissue such as proteoglycans. Nevertheless, these building blocks themselves are not osteoinductive and do not promote the differentiation of MSCs into chondrocytes. In short, these inert building blocks still require the cellular
activation that only BMPs can provide. It is the BMP signaling which activates and differentiates the MSC into chondrocytes for the development, maintenance, and repair of the extracellular matrix (ECM) of cartilage.*

Cyplexinol® is the only food-grade BMP-complex proven to differentiate MSCs, thereby meeting the currently unmet medical need in bone and cartilage management. Additionally, since the BMPs within the complex modulate inflammatory pathways working on Interleukin-1 and Interleukin-6 (IL-1 and IL-6)- this novel agent not only provides the missing osteoinductive signal so traditional nutrients can work properly- but also provide rapid results for joint health.* In a recently published double-blind, placebo controlled trial of 84 subjects, Cyplexinol® - Nature’s BMP-Complex was reported to provide statistically significant clinical improvement in occasional joint discomfort, stiffness and quality of life scores in just 7 days.*

Clinical Trial Results

Further, 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*.

Dr Adam Perlman PhdDr. Adam Perlman was appointed to the position of Executive Director of Duke Integrative Medicine in 2011. In 2010 he became the Chair for the Consortium of Academic Health Centers for Integrative Medicine, a consortium comprising 50 leading academic medical centers around the country with integrative medical programs. Since 2007, Dr. Perlman has been Chairperson for the Department of Primary Care within the School of Health-Related Professions at University of Medicine and Dentistry of New Jersey (UMDNJ). He has held the UMDNJ Hunterdon Endowed Professorship in Complementary and Alternative Medicine since 2004.


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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. 

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