Currently, there is no therapy that can completely stop the progression of OA. There is also no possibility to reverse the effects of already existing changes, thus the available therapies are dedicated only to reduce the symptoms of the disease.

Therefore, recently a search for a solution, based on targeted therapies that act on the molecular signaling levels has become more effective. Unfortunately, previous experience showed that therapy based on interleukin 1 receptor antagonist (IL-1Ra) did not fulfill its first expectations¹. The researchers’ attention has now focused on the Wnt signaling pathway as a one of the major factors responsible for the OA progression². Increased activation of the Wnt signaling pathway plays a major role in the development and progression of OA, by controlling the function of synovial cells, chondrocytes and osteoblasts, so affecting^3,4:

Bone remodeling
Osteoblast apoptosis
Synovium inflammation
Articular cartilage metabolism
Extracellular matrix catabolism

Because of that, the global direction of OA therapy focuses on blocking the overactive canonical Wnt signaling pathway in the synovial joint tissues at the molecular level. Attention has been now focused on natural inhibitors of the Wnt signaling pathway, of which DKK-1 plays an important role⁵.Scientific and clinical data shows that therapy based on Wnt signaling pathway inhibition can be a respectful treatment for joint environment deterioration⁶. DKK-1 protein, acting as an inhibitor, influences the signaling pathway of Wnt by deactivating it. High abundance of DKK-1 protein protects articular cartilage from degradation and finally slows the progression of the osteoarthritis⁷.

Motivated by this Wint™ kit contains a highly efficient separation device, which due to its unique design and presence of carefully selected borosilicate PLT activator allows to separate and isolate a very high number of DKK-1 protein in the final injection product.

As a result, the blood-derived product acquired by Wint™ separation device allows to obtain more than 2x higher DKK-1 protein concentration than in platelet-rich plasma and up to 5x higher DKK-1 protein concentration than can be detected in the plasma of healthy patient’s⁶.

The role of Wnt signaling in OA pathology and progression

Wnt signaling pathway plays a pivotal role in a various processes. The development of the articular joints, including cartilage tissue and joint cavity is one of them¹. Taking this into consideration the occurrence and progression of the degenerative joint diseases, such as osteoarthritis (OA) is described to be linked with Wnt pathway².

Wnt pathway is activated when the Wnt protein ligand binds itself to specific receptors located on the cell membrane of e.g. chondrocytes or synovial like fibroblasts. That action leads to destabilization of the β-catenin degradation complex and what follows, the cumulation of this protein in the cytoplasm. Subsequently, accumulated β-catenin molecules are able to migrate to the cell nuclei (acting as a transcription factors) and by this they influence transcription of wide range of genes, including ones that are responsible for the progression of the OA³.

Therapeutic rationale of DKK-1 protein enriched blood derived product in OA affected joints

Current strategy in OA therapies focuses on blocking the overactive canonical Wnt signaling pathway in the synovial joint tissues at the molecular level. There are numbers of known chemical inhibitors, but DKK-1 is one of the most potent and, what is important, it is endogenously produced Wnt signaling pathway inhibitor.

When DKK-1 protein binds to the Wnt signaling pathway receptor, it blocks the specific binding site of the Wnt ligand protein, preventing further pathway activation. This leads to β-catenin degradation complex activation and further β-catenin molecules degradation. Lack of β-catenin proteins in cell cytoplasm prevents the transcription mechanism activation and the factors responsible for OA progression cannot be produced by the chondrocytes or synovial like fibroblasts⁴.

Interestingly, PLTs are known, rich source of DKK-1 protein. When properly activated and stimulated, platelets can secrete increased amounts of this natural inhibitor. Thus, activated autologous blood-derived products, after the separation and concentration can provide an abundance of Wnt signaling pathway inhibitor. Further intra-articular administration of this can lead to the reduction of the degradation of articular cartilage and diminishing of the joint inflammation⁵.

Intra-articular injection of the product obtained by the Wint™ kit is a highly recommendable therapy for joint associated pathologies. Based on the literature and experience, the therapy which uses autologous blood-derived product enriched with DKK-1 protein was estimated as an therapeutically effective against OA symptoms⁶.

Supporting evidences for the validity of Wnt signaling pathway inhibition by DKK-1 in OA:

In OA patients decreased levels of DKK-1 in plasma and synovial fluid are observed⁷
It has been shown that the level of DKK-1 protein is highly is related to the stage of the osteoarthritis → the higher stage of the disease, the lower concentration of DKK-1 in the patient’s plasma⁷
Increased production of DKK-1 in synovial cells, chondrocytes and osteoblasts protects the articular cartilage from degradation and diminishes the progression of OA^4,7

Materials:

A5_IFU_WNTPL_EN_220090_ONLINE.pdf

B5_REK_WNTEN_220836_6_online.pdf