A light and electron microscopic study of ectopic tendon and ligament formation induced by bone morphogenetic protein–13 adenoviral gene therapy

Helm, Gregory A.; Li, Jin Zhong; Alden, Tord D.; Hudson, Sarah A.; Beres, Elisa J.; Cunningham, Mary; Mikkelsen, Mark M.; Pittman, Debra D.; Kerns, Kelvin M.; Kallmes, David F.

doi:10.3171/foc.2000.8.4.7

Cited by 14 publications

(22 citation statements)

References 37 publications

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“…BMP‐7 encouraged the formation of a denser network of trabecular bone at the reattachment site than was evident in controls. It is also worth noting that BMP‐13 induces neotendon formation with fibrocartilage cell differentiation in skeletal muscle of athymic nude rats (Helm et al. 2001).…”

Section: Enthesis Turnovermentioning

confidence: 99%

Where tendons and ligaments meet bone: attachment sites (‘entheses’) in relation to exercise and/or mechanical load

et al. 2006

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Entheses (insertion sites, osteotendinous junctions, osteoligamentous junctions) are sites of stress concentration at the region where tendons and ligaments attach to bone. Consequently, they are commonly subject to overuse injuries (enthesopathies) that are well documented in a number of sports. In this review, we focus on the structurefunction correlations of entheses on both the hard and the soft tissue sides of the junction. Particular attention is paid to mechanical factors that influence form and function and thus to exploring the relationship between entheses and exercise. The molecular parameters indicative of adaptation to mechanical stress are evaluated, and the basis on which entheses are classified is explained. The application of the 'enthesis organ' concept (a collection of tissues adjacent to the enthesis itself, which jointly serve the common function of stress dissipation) to understanding enthesopathies is considered and novel roles of adipose tissue at entheses are reviewed. A distinction is made between different locations of fat at entheses, and possible functions include space-filling and proprioception. The basic anchorage role of entheses is considered in detail and comparisons are explored between entheses and other biological 'anchorage' sites. The ability of entheses for self-repair is emphasized and a range of enthesopathies common in sport are reviewed (e.g. tennis elbow, golfer's elbow, jumper's knee, plantar fasciitis and Achilles insertional tendinopathies). Attention is drawn to the degenerative, rather than inflammatory, nature of most enthesopathies in sport. The biomechanical factors contributing to the development of enthesopathies are reviewed and the importance of considering the muscle-tendon-bone unit as a whole is recognized. Bony spur formation is assessed in relation to other changes at entheses which parallel those in osteoarthritic synovial joints.

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Section: Enthesis Turnovermentioning

confidence: 99%

Where tendons and ligaments meet bone: attachment sites (‘entheses’) in relation to exercise and/or mechanical load

et al. 2006

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“…Several studies have reported neo-tendon/ligament formation and the development of highly organized connective tissue rich in collagen I fibres in response to in vivo ectopic implantation of BMP13 at sites of tendon wounding in rats 61,69,70 and intramuscularly 60,71. Progenitor cell proliferation and differentiation into neo-tendon/neo-ligament was reported within the muscle, the formation of collagenous extracellular matrix, and even development of small bone and cartilage foci within the new tissue 71.…”

Section: Bmp13 Expression and Functionmentioning

confidence: 99%

“…Progenitor cell proliferation and differentiation into neo-tendon/neo-ligament was reported within the muscle, the formation of collagenous extracellular matrix, and even development of small bone and cartilage foci within the new tissue 71.…”

Section: Bmp13 Expression and Functionmentioning

confidence: 99%

Unveiling the Bmp13 Enigma: Redundant Morphogen or Crucial Regulator?

Williams

Bhargav²,

Diwan³

2008

Int. J. Biol. Sci.

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Bone morphogenetic proteins are a diverse group of morphogens with influences not only on bone tissue, as the nomenclature suggests, but on multiple tissues in the body and often at crucial and influential periods in development.The purpose of this review is to identify and discuss current knowledge of one vertebrate BMP, Bone Morphogenetic Protein 13 (BMP13), from a variety of research fields, in order to clarify BMP13's functional contribution to developing and maintaining healthy tissues, and to identify potential future research directions for this intriguing morphogen. BMP13 is highly evolutionarily conserved (active domain >95%) across diverse species from Zebrafish to humans, suggesting a crucial function. In addition, mutations in BMP13 have recently been associated with Klippel-Feil Syndrome, causative of numerous skeletal and developmental defects including spinal disc fusion. The specific nature of BMP13's crucial function is, however, not yet known.The literature for BMP13 is focused largely on its activity in the healing of tendon-like tissues, or in comparisons with other BMP family molecules for whom a clear function in embryo development or osteogenic differentiation has been identified. There is a paucity of detailed information regarding BMP13 protein activity, structure or protein processing. Whilst some activity in the stimulation of osteogenic or cartilaginous gene expression has been reported, and BMP13 expression is found in post natal cartilage and tendon tissues, there appears to be a redundancy of function in the BMP family, with several members capable of stimulating similar tissue responses. This review aims to summarise the known or potential role(s) for BMP13 in a variety of biological systems.

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“…GDF‐6/BMP‐13 . GDF‐6/BMP‐13 has been shown to stimulate proliferation and collagen production of tendon fibroblasts in vitro (Wong et al , 2005), promote neotendon/neoligament formation after subcutaneous and intramuscular implantation (Helm et al , 2001; Wolfman et al , 1997) and promote tendon repair in vivo (Aspenberg and Forslund, 1999; Forslund and Aspenberg, 2003, 2001; Forslund et al , 2003; Virchenko et al , 2005). The neotendon/neoligament tissue formed in Wolfman et al 's (1997) study resembled matured tendons at both micro‐ and ultrastructural levels and expressed elastin, decorin, collagen type I , sine oculis homeobox homologue 1/2 ( six 1/six 2 ) and aggrecan but not ALP and osteocalcin mRNA, similar to that in developing and matured tendons.…”

Section: Factors Regulating Tenogenic Differentiation Of Stem Cellsmentioning

confidence: 99%

Tenogenic differentiation of stem cells for tendon repair-what is the current evidence?

Lui

Rui

et al. 2011

J Tissue Eng Regen Med

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Tendon/ligament injuries are very common in sports and other rigorous activities. Tendons regenerate and repair slowly and inefficiently in vivo after injury. The limited ability of tendon to self-repair and the general inefficiencies of current treatment regimes have hastened the motivation to develop tissue-engineering strategies for tissue repair. Of particular interest in recent years has been the use of adult mesenchymal stem cells (MSCs) to regenerate functional tendons and ligaments. Different sources of MSCs have been studied for their effects on tendon repair. However, ectopic bone and tumour formation has been reported in some special circumstances after transplantation of MSCs. The induction of MSCs to differentiate into tendon-forming cells in vitro prior to transplantation is a possible approach to avoid ectopic bone and tumour formation while promoting tendon repair. While there are reports about the factors that might promote tenogenic differentiation, the study of tenogenic differentiation is hampered by the lack of definitive biomarkers for tendons. This review aims to summarize the cell sources currently used for tendon repair as well as their advantages and limitations. Factors affecting tenogenic differentiation were summarized. Molecular markers currently used for assessing tenogenic differentiation or neotendon formation are summarized and their advantages and limitations are commented upon. Finally, further directions for promoting and assessing tenogenic differentiation of stem cells for tendon repair are discussed.

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A light and electron microscopic study of ectopic tendon and ligament formation induced by bone morphogenetic protein–13 adenoviral gene therapy

Cited by 14 publications

References 37 publications

Where tendons and ligaments meet bone: attachment sites (‘entheses’) in relation to exercise and/or mechanical load

Where tendons and ligaments meet bone: attachment sites (‘entheses’) in relation to exercise and/or mechanical load

Unveiling the Bmp13 Enigma: Redundant Morphogen or Crucial Regulator?

Tenogenic differentiation of stem cells for tendon repair-what is the current evidence?

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