ABSTRACT:The adult healing response of the rotator cuff tendon-to-bone insertion site differs from the ordered process of insertion site development. Healing is characterized by disorganized scar and a lack of fibrocartilage formation, in contrast to the well organized fibrocartilaginous transition which forms during the normal development of the tendon-to-bone insertion. The purpose of this study was to localize the expression of a number of extracellular matrix and growth factor genes during insertion site development in order to guide future strategies for augmenting adult rotator cuff healing. The rotator cuff was morphologically distinct at 13.5 dpc (days postconception). Neotendon was evident as a condensation of cells adjacent to bone. The interface between tendon and bone did not form into a mature fibrocartilaginous insertion until 21-days postnatally, based upon the appearance of four distinct zones with a mineralized humeral head. Fibroblasts of the supraspinatus tendon expressed type I collagen at all timepoints. Type II collagen was first expressed by chondrocytes in the fibrocartilage and mineralized fibrocartilage at 7 days and persisted in the mineralized fibrocartilage at 56 days. Type X collagen was first expressed by the chondrocytes in the mineralized fibrocartilage at 14 days and persisted in the mineralized fibrocartilage at 56 days. A shift from TGF-b3 to TGF-b1 expression occurred at 15.5 dpc. ß

Tendon is one of the least understood tissues of the musculoskeletal system in terms of development and morphogenesis. Collagen fibrillogenesis has been the most studied aspect of tendon development, focusing largely on the role of matrix molecules such as collagen type III and decorin. While involvement of matrix molecules in collagen fibrillogenesis during chick tendon development is well understood, the role of growth factors has yet to be elucidated. This work examines the expression patterns of transforming growth factor (TGF) -␤1, -␤2, and -␤3, and their receptors with respect to expression patterns of collagen type III, decorin, and fibronectin. We focus on the intermediate stages of tendon development in the chick embryo, a period during which the tendon micro-and macro-architecture are being established. Our findings demonstrate for the first time that TGF-␤1, -␤2, and -␤3 have distinct spatiotemporal developmental protein localization patterns in the developing tendon and strongly suggest that these isoforms have independent roles in tendon development.

This study identifies the IL-25 receptor, IL-17RB, is an important mediator of both innate and adaptive pulmonary type 2 immune responses. Allergen exposure upregulated IL-25 and induced type 2 cytokine production in a novel granulocytic population, termed Type 2 Myeloid (T2M) cells. Il17rb−/− mice exhibited reduced lung pathology following chronic allergen exposure and decreased cytokine production in T2M cells and CD4+ T-lymphocytes. Airway instillation of IL-25 induced IL-4 and IL-13 production exclusively in T2M cells demonstrating their importance in generating T cell-independent inflammation. The adoptive transfer of T2M cells reconstituted IL-25-mediated responses in Il17rb−/− mice. High dose dexamethasone treatment did not reduce the IL-25-induced T2M pulmonary response. Finally, a similar IL-4/IL-13 producing granulocytic population was identified in peripheral blood of asthmatics. These data establish IL-25/IL-17RB as targets for innate and adaptive immune responses in chronic allergic airways disease, and identify T2M cells as a novel steroid-resistant cell population.