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  1. Article ; Online: Advancing basic and preclinical spine research: Highlights from the ORS PSRS 6th International Spine Research Symposium.

    Smith, Lachlan J / Martin, John T / Risbud, Makarand V

    JOR spine

    2023  Volume 6, Issue 4, Page(s) e1308

    Abstract: The sixth biennial ORS PSRS International Spine Research Symposium was held from November 6 to 10, 2022, at Skytop Lodge in northeastern Pennsylvania, USA. Organized jointly by the Orthopaedic Research Society and the Philadelphia Spine Research Society, ...

    Abstract The sixth biennial ORS PSRS International Spine Research Symposium was held from November 6 to 10, 2022, at Skytop Lodge in northeastern Pennsylvania, USA. Organized jointly by the Orthopaedic Research Society and the Philadelphia Spine Research Society, the symposium attracted more than 200 participants from 15 different countries who came together to share the latest advances in basic and preclinical spine research. Following the symposium, selected participants were invited to submit full-length manuscripts to this special issue of
    Language English
    Publishing date 2023-11-21
    Publishing country United States
    Document type Editorial
    ISSN 2572-1143
    ISSN (online) 2572-1143
    DOI 10.1002/jsp2.1308
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Editorial: Cell-based therapeutics for intervertebral disc degeneration.

    Li, Zhen / Smith, Lachlan J / Li, Bin

    Frontiers in bioengineering and biotechnology

    2023  Volume 11, Page(s) 1250266

    Language English
    Publishing date 2023-07-06
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2719493-0
    ISSN 2296-4185
    ISSN 2296-4185
    DOI 10.3389/fbioe.2023.1250266
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Advancing basic and preclinical spine research: Highlights from the ORS PSRS 5th International Spine Research Symposium.

    Smith, Lachlan J / Iatridis, James C / Dahia, Chitra L

    JOR spine

    2020  Volume 3, Issue 4, Page(s) e1134

    Abstract: The fifth biennial ORS PSRS International Spine Research Symposium took place from November 3 to 7, 2019, at Skytop Lodge in northeastern Pennsylvania. Organized jointly by the Orthopaedic Research Society and the Philadelphia Spine Research Society, the ...

    Abstract The fifth biennial ORS PSRS International Spine Research Symposium took place from November 3 to 7, 2019, at Skytop Lodge in northeastern Pennsylvania. Organized jointly by the Orthopaedic Research Society and the Philadelphia Spine Research Society, the symposium attracted more than 180 participants from 10 different countries to share the latest advances in basic and preclinical spine research. Following the symposium, participants were invited to submit full-length manuscripts to this special issue of JOR Spine.
    Language English
    Publishing date 2020-12-02
    Publishing country United States
    Document type Editorial
    ISSN 2572-1143
    ISSN (online) 2572-1143
    DOI 10.1002/jsp2.1134
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Quantifying a novel three-dimensional marker of scoliosis.

    Arginteanu, Toren / Gallagher, Ryan S / Borja, Austin J / Glauser, Gregory / Smith, Lachlan J / Pasha, Saba / DeTurck, Dennis / Malhotra, Neil R

    Spine deformity

    2023  Volume 12, Issue 1, Page(s) 231–237

    Abstract: Background: Scoliosis causes abnormal spinal curvature and torsional rotation of the vertebrae and has implications for human suffering and societal cost. In differential geometry, Writhe describes three-dimensional curvature. Differential geometric ... ...

    Abstract Background: Scoliosis causes abnormal spinal curvature and torsional rotation of the vertebrae and has implications for human suffering and societal cost. In differential geometry, Writhe describes three-dimensional curvature. Differential geometric quantities can inform better diagnostic metrics of scoliotic deformity. This evaluation could help physicians and researchers study scoliosis and determine treatments.
    Methods: Eight adult lumbar spine CT scans were analyzed in custom MATLAB programs to estimate Writhe and Cobb angle. Five patients exhibited scoliotic curvature, and three controls were asymptomatic. Vertebral centroids in three-dimensional space were determined, and Writhe was approximated. A T-test determined whether the affected spines had greater Writhe than the controls. Cohen's D test was used to determine effect size.
    Results: Writhe of scoliotic spines (5.4E-4 ± 2.7E-4) was significantly higher than non-scoliotic spines (8.2E-5 ± 1.1E-4; p = 0.008).
    Conclusion: Writhe, a measure of curvature derived from 3D imaging, is significantly greater in scoliotic than in non-scoliotic spines. Future directions must include more subjects and examine writhe as a marker of scoliosis severity, progression, and response to treatment.
    MeSH term(s) Adult ; Humans ; Scoliosis/diagnostic imaging ; Spine ; Imaging, Three-Dimensional/methods ; Forecasting
    Language English
    Publishing date 2023-09-22
    Publishing country England
    Document type Journal Article
    ZDB-ID 2717704-X
    ISSN 2212-1358 ; 2212-134X ; 2212-1358
    ISSN (online) 2212-1358 ; 2212-134X
    ISSN 2212-1358
    DOI 10.1007/s43390-023-00752-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Impact of the COVID-19 pandemic on the productivity and career prospects of musculoskeletal researchers.

    Chakraborty, Lauren S / Le Maitre, Christine L / Chahine, Nadeen O / Fields, Aaron J / Gawri, Rahul / Giers, Morgan B / Smith, Lachlan J / Tang, Simon Y / Zehra, Uruj / Haglund, Lisbet / Samartzis, Dino / Martin, John T

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

    2024  

    Abstract: Academic researchers faced a multitude of challenges posed by the COVID-19 pandemic, including widespread shelter-in-place orders, workplace closures, and cessation of in-person meetings and laboratory activities. The extent to which these challenges ... ...

    Abstract Academic researchers faced a multitude of challenges posed by the COVID-19 pandemic, including widespread shelter-in-place orders, workplace closures, and cessation of in-person meetings and laboratory activities. The extent to which these challenges impacted musculoskeletal researchers, specifically, is unknown. We developed an anonymous web-based survey to determine the pandemic's impact on research productivity and career prospects among musculoskeletal research trainees and faculty. There were 116 musculoskeletal (MSK) researchers with varying demographic backgrounds who completed the survey. Of respondents, 48.3% (n = 56) believed that musculoskeletal funding opportunities decreased because of COVID-19, with faculty members more likely to hold this belief compared to nonfaculty researchers (p = 0.008). Amongst MSK researchers, 88.8% (n = 103) reported research activity was limited by COVID-19, and 92.2% (n = 107) of researchers reported their research was not able to be refocused on COVID-19-related topics, with basic science researchers less likely to be able to refocus their research compared to clinical researchers (p = 0.030). Additionally, 47.4% (n = 55) reported a decrease in manuscript submissions since the onset of the pandemic. Amongst 51 trainee researchers, 62.8% (n = 32) reported a decrease in job satisfaction directly attributable to the COVID-19 pandemic. In summary, study findings indicated that MSK researchers struggled to overcome challenges imposed by the pandemic, reporting declines in funding opportunities, research productivity, and manuscript submission. Trainee researchers experienced significant disruptions to critical research activities and worsening job satisfaction. Our findings motivate future efforts to support trainees in developing their careers and target the recovery of MSK research from the pandemic stall.
    Language English
    Publishing date 2024-04-28
    Publishing country United States
    Document type Journal Article
    ZDB-ID 605542-4
    ISSN 1554-527X ; 0736-0266
    ISSN (online) 1554-527X
    ISSN 0736-0266
    DOI 10.1002/jor.25866
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Evaluation of tendon and ligament microstructure and mechanical properties in a canine model of mucopolysaccharidosis I.

    Lau, Yian Khai / Iyer, Keerthana / Shetye, Snehal / Friday, Chet S / Dodge, George R / Hast, Michael W / Casal, Margret L / Gawri, Rahul / Smith, Lachlan J

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

    2024  

    Abstract: Mucopolysaccharidosis (MPS) I is a lysosomal storage disorder characterized by deficient alpha-l-iduronidase activity, leading to abnormal accumulation of glycosaminoglycans (GAGs) in cells and tissues. Synovial joint disease is prevalent and ... ...

    Abstract Mucopolysaccharidosis (MPS) I is a lysosomal storage disorder characterized by deficient alpha-l-iduronidase activity, leading to abnormal accumulation of glycosaminoglycans (GAGs) in cells and tissues. Synovial joint disease is prevalent and significantly reduces patient quality of life. There is a strong clinical need for improved treatment approaches that specifically target joint tissues; however, their development is hampered by poor understanding of underlying disease pathophysiology, including how pathological changes to component tissues contribute to overall joint dysfunction. Ligaments and tendons, in particular, have received very little attention, despite the critical roles of these tissues in joint stability and biomechanical function. The goal of this study was to leverage the naturally canine model to undertake functional and structural assessments of the anterior (cranial) cruciate ligament (CCL) and Achilles tendon in MPS I. Tissues were obtained postmortem from 12-month-old MPS I and control dogs and tested to failure in uniaxial tension. Both CCLs and Achilles tendons from MPS I animals exhibited significantly lower stiffness and failure properties compared to those from healthy controls. Histological examination revealed multiple pathological abnormalities, including collagen fiber disorganization, increased cellularity and vascularity, and elevated GAG content in both tissues. Clinically, animals exhibited mobility deficits, including abnormal gait, which was associated with hyperextensibility of the stifle and hock joints. These findings demonstrate that pathological changes to both ligaments and tendons contribute to abnormal joint function in MPS I, and suggest that effective clinical management of joint disease in patients should incorporate treatments targeting these tissues.
    Language English
    Publishing date 2024-02-18
    Publishing country United States
    Document type Journal Article
    ZDB-ID 605542-4
    ISSN 1554-527X ; 0736-0266
    ISSN (online) 1554-527X
    ISSN 0736-0266
    DOI 10.1002/jor.25813
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Failures of Endochondral Ossification in the Mucopolysaccharidoses.

    Jiang, Zhirui / Byers, Sharon / Casal, Margret L / Smith, Lachlan J

    Current osteoporosis reports

    2020  Volume 18, Issue 6, Page(s) 759–773

    Abstract: Purpose of review: The mucopolysaccharidoses (MPS) are a group of inherited lysosomal storage disorders characterized by abnormal accumulation of glycosaminoglycans (GAGs) in cells and tissues. MPS patients frequently exhibit failures of endochondral ... ...

    Abstract Purpose of review: The mucopolysaccharidoses (MPS) are a group of inherited lysosomal storage disorders characterized by abnormal accumulation of glycosaminoglycans (GAGs) in cells and tissues. MPS patients frequently exhibit failures of endochondral ossification during postnatal growth leading to skeletal deformity and short stature. In this review, we outline the current understanding of the cellular and molecular mechanisms underlying failures of endochondral ossification in MPS and discuss associated treatment challenges and opportunities.
    Recent findings: Studies in MPS patients and animal models have demonstrated that skeletal cells and tissues exhibit significantly elevated GAG storage from early in postnatal life and that this is associated with impaired cartilage-to-bone conversion in primary and secondary ossification centers, and growth plate dysfunction. Recent studies have begun to elucidate the underlying cellular and molecular mechanisms, including impaired chondrocyte proliferation and hypertrophy, diminished growth factor signaling, disrupted cell cycle progression, impaired autophagy, and increased cell stress and apoptosis. Current treatments such as hematopoietic stem cell transplantation and enzyme replacement therapy fail to normalize endochondral ossification in MPS. Emerging treatments including gene therapy and small molecule-based approaches hold significant promise in this regard. Failures of endochondral ossification contribute to skeletal deformity and short stature in MPS patients, increasing mortality and reducing quality of life. Early intervention is crucial for effective treatment, and there is a critical need for new approaches that normalize endochondral ossification by directly targeting affected cells and signaling pathways.
    MeSH term(s) Animals ; Bone Diseases/etiology ; Bone Diseases/physiopathology ; Bone Diseases/therapy ; Growth Disorders/etiology ; Growth Disorders/physiopathology ; Humans ; Mucopolysaccharidoses/complications ; Mucopolysaccharidoses/physiopathology ; Mucopolysaccharidoses/therapy
    Language English
    Publishing date 2020-10-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2186581-4
    ISSN 1544-2241 ; 1544-1873
    ISSN (online) 1544-2241
    ISSN 1544-1873
    DOI 10.1007/s11914-020-00626-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Single Cell RNA Sequencing Reveals Emergent Notochord-Derived Cell Subpopulations in the Postnatal Nucleus Pulposus.

    Zhang, Chenghao / Zhong, Leilei / Lau, Yian Khai / Wu, Meilun / Yao, Lutian / Schaer, Thomas P / Mauck, Robert L / Malhotra, Neil R / Qin, Ling / Smith, Lachlan J

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Intervertebral disc degeneration is a leading cause of chronic low back pain. Cell-based strategies that seek to treat disc degeneration by regenerating the central nucleus pulposus hold significant promise, but key challenges remain. One of these is the ...

    Abstract Intervertebral disc degeneration is a leading cause of chronic low back pain. Cell-based strategies that seek to treat disc degeneration by regenerating the central nucleus pulposus hold significant promise, but key challenges remain. One of these is the inability of therapeutic cells to effectively mimic the performance of native nucleus pulposus cells, which are unique amongst skeletal cell types in that they arise from the embryonic notochord. In this study we use single cell RNA sequencing to demonstrate emergent heterogeneity amongst notochord-derived nucleus pulposus cells in the postnatal mouse disc. Specifically, we established the existence of early and late stage nucleus pulposus cells, corresponding to notochordal progenitor and mature cells, respectively. Late stage cells exhibited significantly higher expression levels of extracellular matrix genes including aggrecan, and collagens II and VI, along with elevated TGF-β and PI3K-Akt signaling. Additionally, we identified Cd9 as a novel surface marker of late stage nucleus pulposus cells, and demonstrated that these cells were localized to the nucleus pulposus periphery, increased in numbers with increasing postnatal age, and co-localized with emerging glycosaminoglycan-rich matrix. Finally, we used a goat model to show the Cd9+ nucleus pulposus cell numbers decrease with moderate severity disc degeneration, suggesting that these cells are associated with maintenance of the healthy nucleus pulposus extracellular matrix. Improved understanding of the developmental mechanisms underlying regulation of ECM deposition in the postnatal NP may inform improved regenerative strategies for disc degeneration and associated low back pain.
    Language English
    Publishing date 2023-05-22
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.05.21.541589
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Proteomics identifies novel biomarkers of synovial joint disease in a canine model of mucopolysaccharidosis I.

    Zhang, Chenghao / Gawri, Rahul / Lau, Yian Khai / Spruce, Lynn A / Fazelinia, Hossein / Jiang, Zhirui / Jo, Stephanie Y / Scanzello, Carla R / Mai, Wilfried / Dodge, George R / Casal, Margret L / Smith, Lachlan J

    Molecular genetics and metabolism

    2023  Volume 138, Issue 2, Page(s) 107371

    Abstract: Mucopolysaccharidosis I is a lysosomal storage disorder characterized by deficient alpha-L-iduronidase activity, leading to abnormal accumulation of glycosaminoglycans in cells and tissues. Synovial joint disease is prevalent and significantly reduces ... ...

    Abstract Mucopolysaccharidosis I is a lysosomal storage disorder characterized by deficient alpha-L-iduronidase activity, leading to abnormal accumulation of glycosaminoglycans in cells and tissues. Synovial joint disease is prevalent and significantly reduces patient quality of life. There is a critical need for improved understanding of joint disease pathophysiology in MPS I, including specific biomarkers to predict and monitor joint disease progression, and response to treatment. The objective of this study was to leverage the naturally-occurring MPS I canine model and undertake an unbiased proteomic screen to identify systemic biomarkers predictive of local joint disease in MPS I. Synovial fluid and serum samples were collected from MPS I and healthy dogs at 12 months-of-age, and protein abundance characterized using liquid chromatography tandem mass spectrometry. Stifle joints were evaluated postmortem using magnetic resonance imaging (MRI) and histology. Proteomics identified 40 proteins for which abundance was significantly correlated between serum and synovial fluid, including markers of inflammatory joint disease and lysosomal dysfunction. Elevated expression of three biomarker candidates, matrix metalloproteinase 19, inter-alpha-trypsin inhibitor heavy-chain 3 and alpha-1-microglobulin, was confirmed in MPS I cartilage, and serum abundance of these molecules was found to correlate with MRI and histological degenerative grades. The candidate biomarkers identified have the potential to improve patient care by facilitating minimally-invasive, specific assessment of joint disease progression and response to therapeutic intervention.
    MeSH term(s) Dogs ; Animals ; Mucopolysaccharidosis I/pathology ; Proteomics ; Quality of Life ; Joint Diseases/metabolism ; Synovial Fluid/metabolism ; Biomarkers/metabolism ; Disease Progression
    Chemical Substances Biomarkers
    Language English
    Publishing date 2023-01-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1418518-0
    ISSN 1096-7206 ; 1096-7192
    ISSN (online) 1096-7206
    ISSN 1096-7192
    DOI 10.1016/j.ymgme.2023.107371
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Single cell RNA sequencing reveals emergent notochord-derived cell subpopulations in the postnatal nucleus pulposus.

    Zhang, Chenghao / Zhong, Leilei / Lau, Yian Khai / Wu, Meilun / Yao, Lutian / Schaer, Thomas P / Mauck, Robert L / Malhotra, Neil R / Qin, Ling / Smith, Lachlan J

    FASEB journal : official publication of the Federation of American Societies for Experimental Biology

    2023  Volume 38, Issue 1, Page(s) e23363

    Abstract: Intervertebral disc degeneration is a leading cause of chronic low back pain. Cell-based strategies that seek to treat disc degeneration by regenerating the central nucleus pulposus (NP) hold significant promise, but key challenges remain. One of these ... ...

    Abstract Intervertebral disc degeneration is a leading cause of chronic low back pain. Cell-based strategies that seek to treat disc degeneration by regenerating the central nucleus pulposus (NP) hold significant promise, but key challenges remain. One of these is the inability of therapeutic cells to effectively mimic the performance of native NP cells, which are unique amongst skeletal cell types in that they arise from the embryonic notochord. In this study, we use single cell RNA sequencing to demonstrate emergent heterogeneity amongst notochord-derived NP cells in the postnatal mouse disc. Specifically, we established the existence of progenitor and mature NP cells, corresponding to notochordal and chondrocyte-like cells, respectively. Mature NP cells exhibited significantly higher expression levels of extracellular matrix (ECM) genes including aggrecan, and collagens II and VI, along with elevated transforming growth factor-beta and phosphoinositide 3 kinase-protein kinase B signaling. Additionally, we identified Cd9 as a novel surface marker of mature NP cells, and demonstrated that these cells were localized to the NP periphery, increased in numbers with increasing postnatal age, and co-localized with emerging glycosaminoglycan-rich matrix. Finally, we used a goat model to show that Cd9+ NP cell numbers decrease with moderate severity disc degeneration, suggesting that these cells are associated with maintenance of the healthy NP ECM. Improved understanding of the developmental mechanisms underlying regulation of ECM deposition in the postnatal NP may inform improved regenerative strategies for disc degeneration and associated low back pain.
    MeSH term(s) Mice ; Animals ; Nucleus Pulposus/metabolism ; Intervertebral Disc Degeneration/genetics ; Intervertebral Disc Degeneration/metabolism ; Intervertebral Disc/metabolism ; Notochord/metabolism ; Low Back Pain/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Sequence Analysis, RNA
    Chemical Substances Phosphatidylinositol 3-Kinases (EC 2.7.1.-)
    Language English
    Publishing date 2023-12-11
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 639186-2
    ISSN 1530-6860 ; 0892-6638
    ISSN (online) 1530-6860
    ISSN 0892-6638
    DOI 10.1096/fj.202301217R
    Database MEDical Literature Analysis and Retrieval System OnLINE

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