Knockout of hyaluronan synthase 1, but not 3, impairs formation of the retrocalcaneal bursa.

Hyaluronan (HA), a high molecular weight non-sulfated glycosaminoglycan, is an integral component of the extracellular matrix of developing and mature connective tissues including tendon. There are few published reports quantifying HA content during tendon growth and maturation, or detailing its effects on the mechanical properties of the tendon extracellular matrix. Therefore, the goal of the current study was to examine the role of HA synthesis during post-natal skeletal growth and maturation, and its influence on tendon structure and biomechanical function. For this purpose, the morphological, biochemical, and mechanical properties of Achilles tendons from wild type (WT) and hyaluronan synthase 1 and 3 deficient mouse strains (Has1-/- (Has1KO), Has3-/- (Has3KO), and Has1-/- 3-/- (Has1/3KO)) were determined at 4, 8, and 12 weeks of age. Overall, HAS-deficient mice did not show any marked differences from WT mice in Achilles tendon morphology or in the HA and chondroitin/dermatan sulfate (CS/DS) contents. However, HAS1-deficiency (in the single or Has1/3 double KO) impeded post-natal formation of the retrocalcaneal bursa, implicating HAS1 in regulating HA metabolism by cells lining the bursal cavity. Together, these data suggest that HA metabolism via HAS1 and HAS3 does not markedly influence the extracellular matrix structure or function of the tendon body, but plays a role in the formation/maintenance of peritendinous bursa. Additional studies are warranted to elucidate the relationship of HA and CS/DS metabolism to tendon healing and repair in vivo. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2622-2632, 2018.

Tissue and epithelial cell-specific expression of chicken proto-oncogene c-ros in several organs suggests that it may play roles in their development and mature functions.

Proto-oncogene c-ros codes for a receptor-type protein tyrosine kinase (PTK) sharing high homology with the Drosophila sevenless protein. Recent studies of c-ros expression in mouse by in situ hybridization showed that c-ros was expressed specifically and transiently in the epithelial cells of late embryonic kidney collecting duct and intestine villi. Those investigators suggested that c-ros may play a role in the development of those organelles. In the present study, we have examined the expression profile of c-ros in chicken by RNAase protection and in situ hybridization with riboprobes. Our results showed that in addition to kidney and intestine, low levels of c-ros mRNA could also be detected in lung, testis, thymus and bursa. Expression of c-ros commences during middle to late embryonic stages in those organs and persists into the adult life. In situ hybridization revealed that expression of c-ros was restricted to the epithelial cells of all the tissues examined including kidney, intestine, bursa, thymus and testis. In kidney c-ros was detected in all the epithelial cells of the collecting ducts, in intestine it was detected in the epithelial cells of villi and the underneath crypts. Our finding of c-ros expression in chicken differs from those in mouse in (1) instead of transient expression during the embryonic stage, expression of c-ros in chicken kidney and intestine persists into the adult life and (2) expression of c-ros in renal collecting ducts is not restricted to its growing tips, instead it is expressed in the entire epithelial layer of the ducts. Our results suggest that c-ros may play a role not only in the initial induction events in the organogenesis, but also in the mature function of those organs.