The Tendon and Ligament Specific Progenitors and Differentiation Factors

Many of the recent studies have demonstrated that the bMSCs accelerate and improve tendon repair. However, these studies also verified that it is difficult to fully regenerate a tendon. The neo-tendons were similar to the native tendon but were not identical to the native tendon. This outcome may be due to two reasons. One is that the regeneration ability of tendon tissue is limited, unlike bone which can heal by regenerating normal bone in most instances, as an injured tendon often heal by scar tissue; the other reason is the lack of knowledge concerning the tendon tissue specific differentiation factors, say for example in bone regeneration, one of the specific differentiation factors is BMP-2. In order to achieve success in tendon and ligament regeneration, further studies need to be performed to gain more knowledge on the tendon and ligament biology and healing mechanism, as well as their progenitors and specific differentiation factors.

Although many aspects of the biology and biomechanics of tendons and ligaments have been known for some time, there are still basic aspects of tendon and ligaments, such as the developmental process of the tissue, that has not been fully understood.38 It is known that development of the skeleton is a stepwise set of processes, which include the migration of cells to the site of future skeletogenesis, tissue interaction, cell condensation and overt differentiation. So it is suggested that tendons and ligaments develop in similar ways, i.e. from the same initial population of mesodermal cells as the skeleton. In fact, nothing was known about the embryonic origin of tendons, until a recent paper by Brent and colleagues in which they track the origin of tendon progenitors of the body axis and reveal the molecular events as well as the tissue interactions leading to their commitment. They demonstrated that the tendons associated with the axial skeleton derive from an unappreciated, fourth compartment of the somites. Scleraxis (Scx), a bHLH transcription factor, marks this somitic tendon progenitor population. Two earlier-formed somitic compartments, i.e. the sclerotome and myotome, interact to establish this fourth Scx-positive compartment.39'40 Numerous studies have tried to define the role of growth factors in ligament and tendon healing and determine appropriate strategies for the use of growth factors in tissue engineering for tendon and ligament. Various growth factors have been shown to have the ability to improve tendon and ligament cells proliferation or matrix formation. However, little is known about the regulatory signals involved in tendon and ligament differentiation. Wolfman etal.41 reported that GDF-5, 6 (BMP-12 and 13) induced ectopic tendon and ligament-like tissue formation in mice, but this phenomenon will have to be investigated in larger animal models.42 43

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