Tendon-to-bone attachment: From development to maturity

• Published in: Birth defects research. Part C. Embryo today Vol. 102; no. 1; pp. 101 - 112
• Main Authors: Zelzer, Elazar, Blitz, Einat, Killian, Megan L., Thomopoulos, Stavros
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.03.2014; Wiley Subscription Services, Inc
• Subjects: Animals; Attachment; Birth defects; BMP4; bone; Bone and Bones - cytology; Bone and Bones - physiology; bone eminence; Bone growth; cartilage; Chondrocytes; Chondrogenesis; Congenital defects; Control theory; Embryos; enthesis; Feedback loops; Fibroblasts; Growth factors; Humans; IHH; Load transfer; Mineralization; Muscles; musculoskeletal development; Musculoskeletal Physiological Phenomena; Parathyroid; Parathyroid hormone; Phenotypes; Proteins; PTHrP; SCX; Signaling; Skeleton; Sox9 protein; tendon insertion; Tendons - cytology; Tendons - physiology; Tissues; Transforming growth factor-b; BMP4; musculoskeletal development; tendon insertion; bone eminence; cartilage; IHH; SCX; bone; enthesis; PTHrP
• ISSN: 1542-975X; 1542-9768; 1542-9768
• DOI: 10.1002/bdrc.21056

The attachment between tendon and bone occurs across a complex transitional tissue that minimizes stress concentrations and allows for load transfer between muscles and skeleton. This unique tissue cannot be reconstructed following injury, leading to high incidence of recurrent failure and stressing the need for new clinical approaches. This review describes the current understanding of the development and function of the attachment site between tendon and bone. The embryonic attachment unit, namely, the tip of the tendon and the bone eminence into which it is inserted, was recently shown to develop modularly from a unique population of Sox9‐ and Scx‐positive cells, which are distinct from tendon fibroblasts and chondrocytes. The fate and differentiation of these cells is regulated by transforming growth factor beta and bone morphogenetic protein signaling, respectively. Muscle loads are then necessary for the tissue to mature and mineralize. Mineralization of the attachment unit, which occurs postnatally at most sites, is largely controlled by an Indian hedgehog/parathyroid hormone‐related protein feedback loop. A number of fundamental questions regarding the development of this remarkable attachment system require further study. These relate to the signaling mechanism that facilitates the formation of an interface with a gradient of cellular and extracellular phenotypes, as well as to the interactions between tendon and bone at the point of attachment. Birth Defects Research (Part C) 102:101–112, 2014. © 2014 Wiley Periodicals, Inc.