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Primary cilia are highly oriented with respect to collagen direction and long axis of extensor tendon.

ABSTRACT: Skeletal tissues adapt to their mechanical environments by modulating gene expression, cell metabolism, and extracellular matrix (ECM) architecture; however, the mechanosensory mechanisms for these processes are incompletely understood. Primary cilia have emerged as critical components of the cellular mechanosensory apparatus and have been hypothesized to participate in establishment of cellular and ECM orientation, but their function in skeletal tissues is just beginning to be examined. Here we focused on tendon, a tissue with an oriented matrix that is ideal for analysis of spatial relationships between primary cilia and the ECM. The objective of this study was to characterize the incidence and orientation of tenocyte primary cilia in their native ECM. Primary cilia, nuclei, and collagen were analyzed three-dimensionally in immunofluorescently labeled rat extensor tendon using multiphoton microscopy and semiautomated morphometry. Primary cilia were observed in 64% of tenocytes. The cilia were highly oriented with respect to the ECM: cilia were aligned parallel to the collagen fibers and the long axis of the tendon. This study represents the first quantification of the in situ incidence and orientation of primary cilia in tendon.

SUBMITTER: Donnelly E

PROVIDER: S-EPMC2847399 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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Primary cilia are highly oriented with respect to collagen direction and long axis of extensor tendon.

Donnelly Eve E Ascenzi Maria-Grazia MG Farnum Cornelia C

Journal of orthopaedic research : official publication of the Orthopaedic Research Society 20100101 1

Skeletal tissues adapt to their mechanical environments by modulating gene expression, cell metabolism, and extracellular matrix (ECM) architecture; however, the mechanosensory mechanisms for these processes are incompletely understood. Primary cilia have emerged as critical components of the cellular mechanosensory apparatus and have been hypothesized to participate in establishment of cellular and ECM orientation, but their function in skeletal tissues is just beginning to be examined. Here we ...[more]

PMID: 19603516

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Project description:BACKGROUND:While some traumatic closed index extensor tendon ruptures at the musclotendinous junction have been previously reported, closed index extensor tendon pseudorupture due to intertendinous attenuation is exceedingly rare with only one case report of a gymnastics-related sports injury in the English literature. Herein, we report two non-sports injury related cases of traumatic index extensor tendon attenuation mimicking closed tendon rupture, including the pathological findings and intraoperative video of the attenuated extensor indicis proprius tendon. CASE PRESENTATION:A 28-year-old man and a 30-year-old man caught their hands in a high-speed drill and lathe, respectively, which caused a sudden forced flexion of their wrists. They could not actively extend the metacarpophalangeal joints of their index fingers. Intraoperatively, although the extensor indicis proprius and index extensor digitorum communes tendons were in continuity without ruptures, both tendons were attenuated and stretched. The attenuated index extensor tendons were reconstructed either with shortening by plication or step-cut when the tendon damage was less severe or, in severely attenuated tendons, with tendon grafting (ipsilateral palmaris longus) or tendon transfer. Six months after the operation, the active extension of the index metacarpophalangeal joints had recovered well. CONCLUSIONS:Two cases of traumatic index extensor tendon attenuation were treated successfully by shortening the attenuated tendon in combination with tendon graft or transfer. We recommend WALANT (wide-awake local anesthesia and no tourniquet) in the reconstruction surgery of index extensor tendon attenuation to determine the appropriate amount of tendon shortening or optimal tension for tendon grafting or transfer. Intraoperative voluntary finger movement is essential, as it is otherwise difficult to judge the stretch length of intratendinous elongation and extent of traumatic intramuscular damage affecting tendon excursion.

Project description:BackgroundThe primary cilia (PC) is a microtubule-based and nonmotile organelle which protrudes from the surface of almost all mammalian cells. At present, PC has been found to be a deficiency or loss in multiple cancers. Restoring PC could be a novel targeting therapy strategy. Our research showed that PC was reduced in human bladder cancer (BLCA) cells, and PC deficiency promotes cell proliferation. However, the concrete mechanisms remain unknown. SCL/TAL1 interrupting locus (STIL), a PC-related protein, was screened in our previous study and could influence the cell cycle by regulating PC in tumor cells. In this study, we aimed to elucidate the function of STIL for PC to explore the underlying mechanism of PC in BLCA.MethodsPublic database analysis, western blot, and enzyme-linked immunosorbent assay (ELISA) were used to screen genes and explore gene expression alteration. Immunofluorescence and western blot were utilized to investigate PC. Wound healing assay, clone formation assay, and CCK-8 assay were used to explore cell migration, growth, and proliferation. The co-immunoprecipitation and western blot were employed to reveal the interaction of STIL and AURKA.ResultsWe found that high STIL expression is correlated with poor outcomes of BLCA patients. Further analysis revealed that STIL overexpression could inhibit PC formation, activate SHH signaling pathways, and promote cell proliferation. In contrast, STIL-knockdown could promote PC formation, inactivate SHH signaling, and inhibit cell proliferation. Furthermore, we found that the regulatory functions of STIL for PC depend on AURKA. STIL could influence proteasome activity and maintain AURKA stabilization. AURKA-knockdown could reverse PC deficiency caused by STIL overexpression for PC in BLCA cells. We observed that co-knockdown in STIL and AURKA significantly enhanced PC assembly.ConclusionIn summary, our result provides a potential therapy target for BLCA based on the restoration of PC.

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Primary cilia are highly oriented with respect to collagen direction and long axis of extensor tendon.

Publications

Primary cilia are highly oriented with respect to collagen direction and long axis of extensor tendon.

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