रुमेटोलॉजी: वर्तमान शोध
खुला एक्सेस

अमूर्त

Endochondral Ossification in Cartilage Repair Tissue Hampers Bone Marrow Stimulating Techniques

Gelse K, Beyer , Welsch G and Blanke M

Bone marrow-stimulating techniques are frequently applied to induce cartilage repair. Apart from insufficient chondrogenesis of the ingrowing bone marrow stem cells (BMSCs), these techniques are hampered by excessive ossification with formation of intralesional osteophytes, in which the ingrowing BMSCs tend to undergo the inherent programme of endochondral ossification. Within this programme, the chondrocyte phenotype only represents a transient state that is followed by terminal chondrocyte differentiation and replacement of the cartilaginous tissue by osseous tissue. The transcription factor Runx2 is considered the driving force for endochondral ossification, which integrates signals from growth factors that are released from the bone marrow, including bone morphogenetic proteins(BMPs), fibroblast growth factor-2 and members of the Wnt-family among others.

Anti-hypertrophic factors such as PTHrP or anti-angiogenic proteins including Chondromodulin-I or Thrombospondin-1 can inhibit the endochondral ossification. In addition, antagonists of BMP- and Wnt-signalling can stabilize the non-hypertrophic chondrocyte phenotype. The generation of stable cartilage tissue, however, does not only depend on extracellular factors but also on the fate of the originating cell population. Regardless of the spectrum of specific stimuli, BMSCs are prone to finally become osteocytes rather than chondrocytes. Since there is increasing evidence for epigenetic regulation including DNA methylation and histone modification for cartilage-relevant genes,future studies will have to explore the role of genomic imprinting of adult BMSCs. However, as long as tools that stabilize a chondrocyte-specific phenotype of adult BMSCs are not available in clinical routine, the transplantation of differentiated chondrocytes may remain the method of choice for cartilage repair.