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  1. Article ; Online: Strengthening the case for BMP inhibition as a point of intervention for osteoarthritis.

    Lyons, Karen M / Rosen, Vicki

    Osteoarthritis and cartilage

    2023  Volume 31, Issue 11, Page(s) 1423–1424

    MeSH term(s) Humans ; Bone Morphogenetic Proteins/antagonists & inhibitors ; Osteoarthritis/drug therapy
    Chemical Substances Bone Morphogenetic Proteins
    Language English
    Publishing date 2023-08-23
    Publishing country England
    Document type Editorial ; Research Support, N.I.H., Extramural ; Comment
    ZDB-ID 1167809-4
    ISSN 1522-9653 ; 1063-4584
    ISSN (online) 1522-9653
    ISSN 1063-4584
    DOI 10.1016/j.joca.2023.08.007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: BMPs, TGFβ, and border security at the interzone.

    Lyons, Karen M / Rosen, Vicki

    Current topics in developmental biology

    2019  Volume 133, Page(s) 153–170

    Abstract: Synovial joints enable movement and protect the integrity of the articular cartilage. Joints form within skeletal condensations destined to undergo chondrogenesis. The suppression of this chondrogenic program in the interzone is the first morphological ... ...

    Abstract Synovial joints enable movement and protect the integrity of the articular cartilage. Joints form within skeletal condensations destined to undergo chondrogenesis. The suppression of this chondrogenic program in the interzone is the first morphological sign of joint formation. While we have a fairly good understanding of the essential roles of BMP and TGFβ family members in promoting chondrogenic differentiation in developing skeletal elements, we know very little about how BMP activity is suppressed specifically within the interzone, a crucial step in joint development. The function of the BMP ligand Gdf5 has been especially difficult to decipher. On the one hand, Gdf5 is required to promote chondrogenesis of articular elements. On the other hand, Gdf5 is highly expressed in the joint interzone where chondrogenesis must be suppressed for the formation of many joints. Here we review the evidence that BMP signaling must be suppressed within the joint interzone for joint morphogenesis to progress, and consider how Gdf5 exerts its divergent effects on chondrogenesis and joint formation. We also consider how TGFβ signaling impacts formation of the interzone. Finally, we propose a model whereby Gdf5 exerts distinct effects in the interzone vs. surrounding cartilage based on the repertoire of BMP receptors available in these tissues. Understanding how BMP antagonists and counteracting TGFβ signals intersect with Gdf5 to sculpt the joint interzone is essential for understanding the origin of osteoarthritis and other diseases of joint tissues.
    MeSH term(s) Animals ; Bone Morphogenetic Proteins/metabolism ; Growth Differentiation Factor 5/genetics ; Humans ; Joints/embryology ; Joints/metabolism ; Models, Biological ; Signal Transduction ; Transforming Growth Factor beta/metabolism
    Chemical Substances Bone Morphogenetic Proteins ; Growth Differentiation Factor 5 ; Transforming Growth Factor beta
    Language English
    Publishing date 2019-03-01
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 1557-8933 ; 0070-2153
    ISSN (online) 1557-8933
    ISSN 0070-2153
    DOI 10.1016/bs.ctdb.2019.02.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: TGFβ as a gatekeeper of BMP action in the developing growth plate.

    Wang, Weiguang / Rigueur, Diana / Lyons, Karen M

    Bone

    2020  Volume 137, Page(s) 115439

    Abstract: The ligands that comprise the Transforming Growth Factor β superfamily highly govern the development of the embryonic growth plate. Members of this superfamily activate canonical TGFβ and/or BMP (Bone Morphogenetic Protein) signaling pathways. How these ... ...

    Abstract The ligands that comprise the Transforming Growth Factor β superfamily highly govern the development of the embryonic growth plate. Members of this superfamily activate canonical TGFβ and/or BMP (Bone Morphogenetic Protein) signaling pathways. How these pathways interact with one another is an area of active investigation. These two signaling pathways have been described to negatively regulate one another through crosstalk involving Smad proteins, the primary intracellular effectors of canonical signaling. More recently, a mechanism for regulation of the BMP pathway through TGFβ and BMP receptor interactions has been described. Here in this review, we demonstrate examples of how TGFβ is a gatekeeper of BMP action in the developing growth plate at both the receptor and transcriptional levels.
    MeSH term(s) Animals ; Bone Morphogenetic Proteins/metabolism ; Growth Plate/metabolism ; Humans ; Signal Transduction ; Smad Proteins ; Transforming Growth Factor beta/metabolism
    Chemical Substances Bone Morphogenetic Proteins ; Smad Proteins ; Transforming Growth Factor beta
    Language English
    Publishing date 2020-05-20
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 632515-4
    ISSN 1873-2763 ; 8756-3282
    ISSN (online) 1873-2763
    ISSN 8756-3282
    DOI 10.1016/j.bone.2020.115439
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Novel bisphosphonate-based cathepsin K-triggered compound targets the enthesis without impairing soft tissue-to-bone healing.

    Shi, Brendan Y / Sriram, Varun / Wu, Shannon Y / Huang, Dave / Cheney, Alexis / Metzger, Melodie F / Sundberg, Oskar / Lyons, Karen M / McKenna, Charles E / Nishimura, Ichiro / Kremen, Thomas J

    Frontiers in bioengineering and biotechnology

    2024  Volume 12, Page(s) 1308161

    Abstract: Background: ...

    Abstract Background:
    Language English
    Publishing date 2024-02-16
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2719493-0
    ISSN 2296-4185
    ISSN 2296-4185
    DOI 10.3389/fbioe.2024.1308161
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Characterization of bone morphology in CCN5/WISP5 knockout mice.

    Jiang, Jie / Zhao, Gexin / Lyons, Karen M

    Journal of cell communication and signaling

    2018  Volume 12, Issue 1, Page(s) 265–270

    Abstract: CCN5/WISP2 is part of the CCN family of matricellular proteins, but is distinct in that it lacks the C-terminal (CT) domain. Although CCN5 has been shown to impact cell proliferation and differentiation in vitro, its role in vivo is unclear. We therefore ...

    Abstract CCN5/WISP2 is part of the CCN family of matricellular proteins, but is distinct in that it lacks the C-terminal (CT) domain. Although CCN5 has been shown to impact cell proliferation and differentiation in vitro, its role in vivo is unclear. We therefore generated mice using ES cells developed by the Knockout Mouse Project (KOMP) in which exons 2-5, which encode the all of the conserved protein coding regions, are replaced by a lacZ cassette. Ccn5
    Language English
    Publishing date 2018-02-02
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2299380-0
    ISSN 1873-961X ; 1873-9601
    ISSN (online) 1873-961X
    ISSN 1873-9601
    DOI 10.1007/s12079-018-0457-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Whole-mount skeletal staining.

    Rigueur, Diana / Lyons, Karen M

    Methods in molecular biology (Clifton, N.J.)

    2014  Volume 1130, Page(s) 113–121

    Abstract: The first step in almost every investigation of skeletal phenotypes is analysis of whole-mount skeletal preparations. Whole-mount skeletal staining permits evaluation of the shapes and sizes of skeletal elements in their appropriate locations. The ... ...

    Abstract The first step in almost every investigation of skeletal phenotypes is analysis of whole-mount skeletal preparations. Whole-mount skeletal staining permits evaluation of the shapes and sizes of skeletal elements in their appropriate locations. The technique is thus the major method for detecting changes in skeletal patterning. Because cartilage and bone can be distinguished by differential staining, this technique is also a powerful means to assess the pace of skeletal maturation. This protocol covers staining of the pre- and postnatal mouse skeleton using Alcian blue and Alizarin red to identify cartilage and bone, respectively.
    MeSH term(s) Animals ; Bone and Bones/embryology ; Bone and Bones/metabolism ; Female ; Fetus/metabolism ; Histocytological Preparation Techniques ; Mice ; Microscopy/methods ; Pregnancy ; Staining and Labeling/methods
    Language English
    Publishing date 2014-01-31
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-62703-989-5_9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Design and Analysis of CCN Gene Activity Using CCN Knockout Mice Containing LacZ Reporters.

    Jiang, Jie / Hu, Zhengshan / Lyons, Karen M

    Methods in molecular biology (Clifton, N.J.)

    2017  Volume 1489, Page(s) 325–345

    Abstract: Two developments have greatly facilitated the construction of CCN mutant mouse strains. The first is the availability of modified embryonic stem (ES) cells and mice developed through several large-scale government-sponsored research programs. The second ... ...

    Abstract Two developments have greatly facilitated the construction of CCN mutant mouse strains. The first is the availability of modified embryonic stem (ES) cells and mice developed through several large-scale government-sponsored research programs. The second is the advent of CRISPR/Cas9 technology. In this chapter, we describe the available mouse strains generated by gene targeting techniques and the CCN targeting vectors and genetically modified ES cells that are available for the generation of CCN mutant mice. Many of these mutant mouse lines and ES cells carry a β-galactosidase reporter that can be used to track CCN expression, facilitating phenotypic analysis and revealing new sites of CCN action. Therefore, we also describe a method for β-galactosidase staining.
    Language English
    Publishing date 2017
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-4939-6430-7_28
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Correction to: Characterization of bone morphology in CCN5/WISP2 knockout mice.

    Jiang, Jie / Zhao, Gexin / Lyons, Karen M

    Journal of cell communication and signaling

    2017  Volume 12, Issue 1, Page(s) 271

    Abstract: In the original publication's title CCN5/WISP5 should have been CCN5/WISP2. ...

    Abstract In the original publication's title CCN5/WISP5 should have been CCN5/WISP2.
    Language English
    Publishing date 2017-03-31
    Publishing country Netherlands
    Document type Published Erratum
    ZDB-ID 2299380-0
    ISSN 1873-961X ; 1873-9601
    ISSN (online) 1873-961X
    ISSN 1873-9601
    DOI 10.1007/s12079-018-0463-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Biologically-coupled bisphosphonate chaperones effectively deliver molecules to the site of soft tissue-bone healing.

    Kremen, Thomas J / Shi, Brendan Y / Wu, Shannon Y / Sundberg, Oskar / Sriram, Varun / Kim, Won / Sheyn, Dmitriy / Lyons, Karen M / Wang, Weiguang / McKenna, Charles E / Nishimura, Ichiro

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

    2023  Volume 41, Issue 10, Page(s) 2250–2260

    Abstract: Tendon injuries are common and often treated surgically, however, current tendon repair healing results in poorly organized fibrotic tissue. While certain growth factors have been reported to improve both the strength and organization of the repaired ... ...

    Abstract Tendon injuries are common and often treated surgically, however, current tendon repair healing results in poorly organized fibrotic tissue. While certain growth factors have been reported to improve both the strength and organization of the repaired enthesis, their clinical applicability is severely limited due to a lack of appropriate delivery strategies. In this study, we evaluated a recently developed fluorescent probe, Osteoadsorptive Fluorogenic Sentinel-3 that is composed of a bone-targeting bisphosphonate (BP) moiety linked to fluorochrome and quencher molecules joined via a cathepsin K-sensitive peptide sequence. Using a murine Achilles tendon-to-bone repair model, BP-based and/or Ctsk-coupled imaging probes were applied either locally or systemically. Fluorescence imaging was used to quantify the resultant signal in vivo. After tendon-bone repair, animals that received either local or systemic administration of imaging probes demonstrated significantly higher fluorescence signal at the repair site compared to the sham surgery group at all time points (p < 0.001), with signal peaking at 7-10 days after surgery. Our findings demonstrate the feasibility of using a novel BP-based targeting and Ctsk-activated delivery of molecules to the site of tendon-to-bone repair and creates a foundation for further development of this platform as an effective strategy to deliver bioactive molecules to sites of musculoskeletal injury.
    MeSH term(s) Rats ; Animals ; Mice ; Wound Healing ; Rats, Sprague-Dawley ; Tendon Injuries/diagnostic imaging ; Tendon Injuries/drug therapy ; Tendon Injuries/surgery ; Tendons/surgery ; Plastic Surgery Procedures
    Language English
    Publishing date 2023-05-08
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 605542-4
    ISSN 1554-527X ; 0736-0266
    ISSN (online) 1554-527X
    ISSN 0736-0266
    DOI 10.1002/jor.25579
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  10. Article ; Online: Acute infectious laryngitis: A case series.

    Jaworek, Aaron J / Earasi, Kranthi / Lyons, Karen M / Daggumati, Srihari / Hu, Amanda / Sataloff, Robert T

    Ear, nose, & throat journal

    2018  Volume 97, Issue 9, Page(s) 306–313

    Abstract: Although acute laryngitis is common, it is often managed by primary physicians. Therefore, video images documenting its signs are scarce. This series includes 7 professional voice users who previously had undergone baseline strobovideolaryngscopy (SVL) ... ...

    Abstract Although acute laryngitis is common, it is often managed by primary physicians. Therefore, video images documenting its signs are scarce. This series includes 7 professional voice users who previously had undergone baseline strobovideolaryngscopy (SVL) during routine examinations or during evaluations for other complaints and who returned with acute laryngitis. Sequential SVL showed not only the expected erythema, edema, cough, and dysphonia, but also new masses in 5 of the 7 subjects. All the signs returned to baseline. This series is reported to highlight the reversible structural changes that can be expected in patients with acute laryngitis and the value of conservative management.
    MeSH term(s) Acute Disease ; Adolescent ; Adult ; Cough/diagnosis ; Cough/etiology ; Dysphonia/diagnosis ; Dysphonia/etiology ; Erythema/diagnosis ; Erythema/etiology ; Female ; Humans ; Laryngitis/complications ; Laryngitis/diagnosis ; Laryngitis/therapy ; Laryngoscopy/methods ; Male ; Respiratory Tract Infections/complications ; Respiratory Tract Infections/diagnosis ; Respiratory Tract Infections/therapy ; Stroboscopy/methods ; Video Recording ; Young Adult
    Language English
    Publishing date 2018-09-21
    Publishing country United States
    Document type Case Reports ; Journal Article
    ZDB-ID 750153-5
    ISSN 1942-7522 ; 0145-5613
    ISSN (online) 1942-7522
    ISSN 0145-5613
    DOI 10.1177/014556131809700920
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