المؤلفون: Ashley Fung, Mei Sun, Louis J. Soslowsky, David E. Birk

المصدر: Matrix Biology Plus, Vol 16, Iss , Pp 100123- (2022)

مصطلحات موضوعية: Collagen XII, Conditional mouse model, Tendon, Transgenic, Col12a1, Biomechanics, Biology (General), QH301-705.5

الوصف: Collagen XII is a fibril-associated collagen with interrupted triple helices (FACIT). This non-fibrillar collagen is a homotrimer composed of three α1(XII) chains assembled into a collagenous molecule with a C terminal collagenous domain and a large N terminal non-collagenous domain. During tendon development and growth, collagen XII is broadly expressed throughout the extracellular matrix and enriched pericellularly around tenocytes. Tendons in a global Col12a1-/- knockout model demonstrated disrupted fibril and fiber structure and disordered tenocyte organization, highlighting the critical regulatory roles of collagen XII in determining tendon structure and function. However, muscle and bone also are affected in the collagen XII knockout model. Therefore, secondary effects on tendon due to involvement of bone and muscle may occur in the global knockout. The global knockout does not allow the definition of intrinsic mechanisms involving collagen XII in tendon versus extrinsic roles involving muscle and bone. To address this limitation, we created and characterized a conditional Col12a1-null mouse model to permit the spatial and temporal manipulation of Col12a1 expression. Collagen XII knockout was targeted to tendons by breeding conditional Col12a1flox/flox mice with Scleraxis-Cre (Scx-Cre) mice to yield a tendon-specific Col12a1-null mouse line, Col12a1Δten/Δten. Both mRNA and protein expression in Col12a1Δten/Δten mice decreased to near baseline levels in flexor digitorum longus tendons (FDL). Collagen XII immuno-localization revealed an absence of reactivity in the tendon proper, but there was reactivity in the cells of the surrounding peritenon. This supports a targeted knockout in tenocytes while peritenon cells from a non-tendon lineage were not targeted and retained collagen XII expression. The tendon-targeted, Col12a1Δten/Δten mice had significantly reduced forelimb grip strength, altered gait and a significant decrease in biomechanical properties. While the observed decrease in tendon modulus suggests that differences in tendon material properties in the absence of Col12a1 expression underlie the functional deficiencies. Together, these findings suggest an intrinsic role for collagen XII critical for development of a functional tendon.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2590028522000230Test; https://doaj.org/toc/2590-0285Test

الوصول الحر: https://doaj.org/article/ddd609a90dc6404d9795319deeef9cbaTest

المؤلفون: Zakary M. Beach, Mihir S. Dekhne, Ashley B. Rodriguez, Stephanie N. Weiss, Thomas H. Adams, Sheila M. Adams, Mei Sun, David E. Birk, Louis J. Soslowsky

المصدر: Matrix Biology Plus, Vol 15, Iss , Pp 100114- (2022)

مصطلحات موضوعية: Tendon, Biomechanics, Decorin, Biglycan, Proteoglycan, Aging, Biology (General), QH301-705.5

الوصف: Decorin and biglycan are two major small leucine-rich proteoglycans (SLRPs) present in the tendon extracellular matrix that facilitate collagen fibrillogenesis, tissue turnover, and cell signal transduction. Previously, we demonstrated that knockout of decorin prevented the decline of tendon mechanical properties that are associated with aging. The objective of this study was to determine the effects of decorin and biglycan knockdown on tendon structure and mechanics in aged tendons using tamoxifen-inducible knockdown models. We hypothesized that the knockdown of decorin and compound knockdown of decorin and biglycan would prevent age-related declines in tendon mechanics and structure compared to biglycan knockdown and wild-type controls, and that these changes would be exacerbated as the tendons progress towards geriatric ages. To achieve this objective, we created tamoxifen-inducible mouse knockdown models to target decorin and biglycan gene inactivation without the abnormal tendon development associated with traditional knockout models. Knockdown of decorin led to increased midsubstance modulus and decreased stress relaxation in aged tendons. However, these changes were not sustained in the geriatric tendons. Knockdown in biglycan led to no changes in mechanics in the aged or geriatric tendons. Contrary to our hypothesis, the compound decorin/biglycan knockdown tendons did not resemble the decorin knockdown tendons, but resulted in increased viscoelastic properties in the aged and geriatric tendons. Structurally, knockdown of SLRPs, except for the 570d I-Dcn-/-/Bgn-/- group, resulted in alterations to the collagen fibril diameter relative to wild-type controls. Overall, this study identified the differential roles of decorin and biglycan throughout tendon aging in the maintenance of tendon structural and mechanical properties and revealed that the compound decorin and biglycan knockdown phenotype did not resemble the single gene decorin or biglycan models and was detrimental to tendon properties throughout aging.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S259002852200014XTest; https://doaj.org/toc/2590-0285Test

الوصول الحر: https://doaj.org/article/78329dac72374b3ebe73282ada16ec88Test

المؤلفون: Na Rae Park, Snehal S. Shetye, Igor Bogush, Douglas R. Keene, Sara Tufa, David M. Hudson, Marilyn Archer, Ling Qin, Louis J. Soslowsky, Nathaniel A. Dyment, Kyu Sang Joeng

المصدر: Scientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)

مصطلحات موضوعية: Medicine, Science

الوصف: Abstract Tendon plays a critical role in the joint movement by transmitting force from muscle to bone. This transmission of force is facilitated by its specialized structure, which consists of highly aligned extracellular matrix consisting predominantly of type I collagen. Tenocytes, fibroblast-like tendon cells residing between the parallel collagen fibers, regulate this specialized tendon matrix. Despite the importance of collagen structure and tenocyte function, the biological mechanisms regulating fibrillogenesis and tenocyte maturation are not well understood. Here we examine the function of Reticulocalbin 3 (Rcn3) in collagen fibrillogenesis and tenocyte maturation during postnatal tendon development using a genetic mouse model. Loss of Rcn3 in tendon caused decreased tendon thickness, abnormal tendon cell maturation, and decreased mechanical properties. Interestingly, Rcn3 deficient mice exhibited a smaller collagen fibril distribution and over-hydroxylation in C-telopeptide cross-linking lysine from α1(1) chain. Additionally, the proline 3-hydroxylation sites in type I collagen were also over-hydroxylated in Rcn3 deficient mice. Our data collectively suggest that Rcn3 is a pivotal regulator of collagen fibrillogenesis and tenocyte maturation during postnatal tendon development.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2045-2322Test

الوصول الحر: https://doaj.org/article/45c74eb3cdcf4f63868318236fda9957Test

المؤلفون: Ryan J. Leiphart, Hai Pham, Tyler Harvey, Taishi Komori, Tina M. Kilts, Snehal S. Shetye, Stephanie N. Weiss, Sheila M. Adams, David E. Birk, Louis J. Soslowsky, Marian F. Young

المصدر: Matrix Biology Plus, Vol 13, Iss , Pp 100099- (2022)

مصطلحات موضوعية: Tendon, Extracellular matrix, Biglycan, Collagen VI, Biomechanics, Collagen fibrils, Biology (General), QH301-705.5

الوصف: Tendon is a vital musculoskeletal tissue that is prone to degeneration. Proper tendon maintenance requires complex interactions between extracellular matrix components that remain poorly understood. Collagen VI and biglycan are two matrix molecules that localize pericellularly within tendon and are critical regulators of tissue properties. While evidence suggests that collagen VI and biglycan interact within the tendon matrix, the relationship between the two molecules and its impact on tendon function remains unknown. We sought to elucidate potential coordinate roles of collagen VI and biglycan within tendon by defining tendon properties in knockout models of collagen VI, biglycan, or both molecules. We first demonstrated co-expression and co-localization of collagen VI and biglycan within the healing tendon, providing further evidence of cooperation between the two molecules during nascent tendon matrix formation. Deficiency in collagen VI and/or biglycan led to significant reductions in collagen fibril size and tendon mechanical properties. However, collagen VI-null tendons displayed larger reductions in fibril size and mechanics than seen in biglycan-null tendons. Interestingly, knockout of both molecules resulted in similar properties to collagen VI knockout alone. These results indicate distinct and non-additive roles for collagen VI and biglycan within tendon. This work provides better understanding of regulatory interactions between two critical tendon matrix molecules.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2590028521000430Test; https://doaj.org/toc/2590-0285Test

الوصول الحر: https://doaj.org/article/8ff4cec26ecb461e91a26fcea0bdab01Test

المؤلفون: Daniel Gittings MD, Corinne Riggin BS, James Boorman-Padgett MS, Stephanie Weiss BS, George Fryhofer MD, MTR, Daniel Farber MD, David Steinberg MD, Louis J. Soslowsky PhD

المصدر: Foot & Ankle Orthopaedics, Vol 4 (2019)

مصطلحات موضوعية: Orthopedic surgery, RD701-811

الوصف: Background: Although nicotine and tobacco use are well established to have adverse health effects, the effects on tendons are less well understood. The purpose of this study was to investigate the effect of chronic nicotine exposure on Achilles tendon (AT) and supraspinatus tendon (SS) physiologic and mechanical properties in a rodent model. Methods: Sprague-Dawley rats (n = 20) were exposed to either 0.9% saline or 36 mg/mL nicotine through an implantable osmotic pump for 12 weeks. At 12 weeks, the AT was imaged in vivo with contrast-enhanced ultrasound (CE-US) to assess vascularity. Bilateral AT and SS were then harvested for ex vivo biomechanical analysis. Statistical analysis was performed using Student t test and Mann Whitney U test. Results: AT CE-US demonstrated a significantly increased wash-in rate in the nicotine group compared to the saline group, indicating an increase in tissue perfusion rate in the nicotine group. AT percent stress relaxation, a measure of tendon viscoelasticity, was significantly increased in the nicotine group compared to the saline group. Similarly, there was a trend toward increased SS percent stress relaxation in the nicotine group compared to the saline group. No differences in other mechanical properties were observed. Conclusion: AT perfusion rate increased and both AT and SS viscoelasticity were altered with chronic nicotine exposure at a clinically relevant dose that models the average smoker in the United States (14 cigarettes per day). Further studies are necessary to link these properties with tendon degeneration and injury. Clinical Relevance: Chronic nicotine exposure affects tendon health. Patients should be counseled as such.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2473-0114Test

الوصول الحر: https://doaj.org/article/c63967534cf245d9a9c01f4c56a01028Test

المؤلفون: Christelle Darrieutort-Laffite, Louis J. Soslowsky, Benoit Le Goff

المصدر: International Journal of Molecular Sciences, Vol 21, Iss 19, p 7000 (2020)

مصطلحات موضوعية: Achilles tendinopathy, ultrasound-guided injections, platelet-rich plasma, stem cells, dry needling, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: Achilles tendinopathy (AT) is a common problem, especially in people of working age, as well as in the elderly. Although the pathogenesis of tendinopathy is better known, therapeutic management of AT remains challenging. Various percutaneous treatments have been applied to tendon lesions: e.g., injectable treatments, platelet-rich plasma (PRP), corticosteroids, stem cells, MMP inhibitors, and anti-angiogenic agents), as well as percutaneous procedures without any injection (percutaneous soft tissue release and dry needling). In this review, we will describe and comment on data about the molecular and structural effects of these treatments obtained in vitro and in vivo and report their efficacy in clinical trials. Local treatments have some impact on neovascularization, inflammation or tissue remodeling in animal models, but evidence from clinical trials remains too weak to establish an accurate management plan, and further studies will be necessary to evaluate their value.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1422-0067/21/19/7000Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/9751dbc1fa734c0ebd72bb9ee0362936Test

المؤلفون: Thomas P. Leahy, Ashley K. Fung, Stephanie N. Weiss, Nathaniel A. Dyment, Louis J. Soslowsky

المصدر: Journal of Orthopaedic Research.

مصطلحات موضوعية: Orthopedics and Sports Medicine

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::92a343d81dc286f739eb424a5ec134a6Test
https://doi.org/10.1002/jor.25590Test

المؤلفون: Zakary M, Beach, Ashley K, Fung, Stephanie N, Weiss, Louis J, Soslowsky

المصدر: Connective Tissue Research. 64:75-81

مصطلحات موضوعية: Rheumatology, Orthopedics and Sports Medicine, Cell Biology, Molecular Biology, Biochemistry

الوصف: A growing interest in the mechanisms that govern tendon healing has resulted in the develop-ment of tools, such as the tamoxifen-inducible mouse knockdown model, to address these questions. However, tamoxifen is a selective estrogen receptor modulator and may interfere with the tendon healing process. The objective of this study was to evaluate the effects of tamoxifen on post-injury tendon mechanics in wild-type mice.The mice underwent treatment at the time of injury using an established mouse injury model and the injured tendons were evaluated 3 weeks post-injury. The treatment contained tamoxifen suspended in corn oil and was compared to a treatment with only corn oil, as well as mice with no treatment. Tendons were evaluated by measuring the quasi-static and viscoelastic mechanics, collagen fiber realignment, cellularity, and nuclear morphology.Mechanical testing of the tendons post-injury revealed no changes to viscoelastic mechanics, quasi-static mechanics, or collagen realignment during loading after tamoxifen treatment with the dosage regimen utilized (three daily injections of 4.5 mg/40 g body weight). Additionally, histological analysis revealed no changes to cellularity or cell nuclear shape.Overall, this study revealed that tamoxifen treatment at the time of tendon injury did not result in changes to tendon mechanics or the histological parameters at 3 weeks post-injury.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bac3bbfceb6a0822fbc9758b9104a196Test
https://doi.org/10.1080/03008207.2022.2097907Test

المؤلفون: Christelle Darrieutort‐Laffite, Zakary M. Beach, Stephanie N. Weiss, Jeremy D. Eekhoff, Louis J. Soslowsky

المصدر: Journal of Orthopaedic Research.

مصطلحات موضوعية: Orthopedics and Sports Medicine

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::100c3963f000c61a9cde3d01e1321fc6Test
https://doi.org/10.1002/jor.25536Test

المؤلفون: Carrie E. Barnum, Snehal S. Shetye, Hossein Fazelinia, Benjamin A. Garcia, Shuyang Fang, Maria Alzamora, Hongyu Li, Lewis M. Brown, Chuanning Tang, Kristin Myers, Ronald Wapner, Louis J. Soslowsky, Joy Y. Vink

المصدر: Reproductive Sciences. 29:1542-1559

مصطلحات موضوعية: Obstetrics and Gynecology

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::f5349e272bda5eea53bac3ae514482c5Test
https://doi.org/10.1007/s43032-022-00892-4Test