Article
Pharmacology & Pharmacy
Weikang Zhang, Yuhang Gong, Xiaohang Zheng, Jianxin Qiu, Ting Jiang, Lihua Chen, Fangying Lu, Xinhui Wu, Fengmin Cheng, Zhenghua Hong
Summary: PDGF-BB promotes extracellular matrix synthesis of NPCs and inhibits pyroptosis, participating in the inhibition of IDD through regulating the MAPK signaling pathway.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Bogdan Costachescu, Adelina-Gabriela Niculescu, Raluca Ioana Teleanu, Bogdan Florin Iliescu, Marius Radulescu, Alexandru Mihai Grumezescu, Marius Gabriel Dabija
Summary: This article introduces the harm of low back pain and the pathogenesis and treatment methods of intervertebral disc degeneration (IDD), focusing on bioactive compounds, cell therapy, and other emerging treatment options.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Marcus Raudner, Markus M. Schreiner, Tom Hilbert, Tobias Kober, Michael Weber, Anna Szelenyi, Reinhard Windhager, Vladimir Juras, Siegfried Trattnig
Summary: The study evaluated GRAPPATINI, an accelerated T-2 mapping sequence that combines undersampling and model-based reconstruction to facilitate clinical implementation of T-2 mapping of the lumbar intervertebral disc. Results showed that T2 values obtained using GRAPPATINI were significantly different for normal discs compared to bulging or herniated discs, as well as discs with and without annular tears. The study concluded that GRAPPATINI can be used as a quantitative imaging biomarker to detect disc pathologies while significantly reducing acquisition time.
EUROPEAN RADIOLOGY
(2021)
Article
Engineering, Biomedical
Xiaoming Zhao, Hongyun Ma, Hao Han, Liuyang Zhang, Jing Tian, Bo Lei, Yingang Zhang
Summary: With the aging population, spinal degeneration seriously affects the quality of life for middle-aged and elderly patients. Injectable biomaterials have gained attention as a minimally invasive and precise repair option for irregular defects. However, the design and functional control of bioactive injectable biomaterials for efficient spinal degeneration treatment remains a challenge.
MATERIALS TODAY BIO
(2022)
Review
Orthopedics
G. Chao-yang, C. Peng, Z. Hai-hong
Summary: This article summarizes the role of the NLRP3 inflammasome in the pathogenesis of IVDD and its application in treatment.
OSTEOARTHRITIS AND CARTILAGE
(2021)
Review
Medicine, Research & Experimental
Chao-yang Gong, Hai-hong Zhang
Summary: Autophagy plays a dual role in intervertebral disc degeneration, as inducing autophagy can slow down the process while excessive autophagy activation-mediated apoptosis may accelerate degeneration.
Review
Cell & Tissue Engineering
Wentao Zhang, Tianze Sun, Ying Li, Ming Yang, Yantao Zhao, Jing Liu, Zhonghai Li
Summary: Stem cell therapy for intervertebral disc degeneration is emerging as a potential treatment option, with evidence from in vitro, in vivo, and clinical trials showing its effectiveness in relieving pain and symptoms, reversing the degenerative cascade, delaying the aging process, and maintaining spinal function. Further research is needed to understand the mechanisms and effects of stem cells in IDD treatment.
STEM CELL RESEARCH & THERAPY
(2022)
Review
Biochemistry & Molecular Biology
Jin-Woo Kim, Neunghan Jeon, Dong-Eun Shin, So-Young Lee, Myongwhan Kim, Dong Hun Han, Jae Yeon Shin, Soonchul Lee
Summary: The intervertebral disc is a complex joint structure with nucleus pulposus, annulus fibrosus, and cartilaginous endplate. Degeneration of the intervertebral disc involves cellular, compositional, and structural changes, with significant alterations in the extracellular matrix composition with age. The hypoxia-inducible factor HIF-1 alpha is crucial in regulating various processes of intervertebral disc degeneration and may serve as a diagnostic tool and therapeutic target for inhibiting this degeneration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Rikuto Yoshimizu, Junsuke Nakase, Katsuhito Yoshioka, Kengo Shimozaki, Kazuki Asai, Mitsuhiro Kimura, Katsuhiko Kitaoka, Hiroyuki Tsuchiya
Summary: This study found that lumbar degeneration was common in children and adolescent weightlifters after 5 years, with 33% of participants showing lumbar disc herniation findings. Long-term high frequency weightlifting training during growth periods may increase the risk of developing low back pain.
Article
Cell Biology
Letizia Penolazzi, Leticia S. Bergamin, Elisabetta Lambertini, Valentina V. Poma, Alba C. Sarti, Pasquale De Bonis, Francesco Di Virgilio, Roberta Piva
Summary: Our study investigated the expression of P2X7 purinergic receptor, NLRP3 inflammasome, and interleukin-1 beta in intervertebral disc specimens at different stages of degeneration, as well as during the dedifferentiation process of primary cells derived from these specimens. The findings suggest that the P2X7R/NLRP3 axis could be a suitable therapeutic target for degenerated disc, as both molecules showed higher expression levels in advanced stages of degeneration. Furthermore, substantial expression of P2X7R was also observed in normal disc tissue, indicating the potential role of P2X7R-mediated purinergic signaling in intervertebral disc metabolism beyond inflammation.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Review
Pharmacology & Pharmacy
Zongtai Liu, Jiabo Zhu, Haiyan Liu, Changfeng Fu
Summary: Intervertebral disc degeneration (IDD) is a common clinical symptom and a significant cause of low back pain. The mechanisms involved in IDD include persistent inflammation, functional cell loss, accelerated extracellular matrix decomposition, imbalance of functional components, and genetic metabolic disorders. Inflammation interacts with other mechanisms and is closely associated with pain production. Natural substances with anti-inflammatory functions offer new options for mitigating degeneration and have potential clinical applications.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Xin Zhang, Shibin Shu, Zhenhua Feng, Yong Qiu, Hongda Bao, Zezhang Zhu
Summary: Stabilization of microtubules promotes the expression of COL2 in nucleus pulposus cells, alleviating disc degeneration. This study identifies microtubule as a promising therapeutic target for IDD and up-regulates COL2 synthesis via the Hippo-Yap pathway. Targeting microtubule acetylation may be an effective strategy for treating IDD.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Medicine, General & Internal
Sebastian Lippross, Paul Girmond, Katja A. Lueders, Friederike Austein, Lena Braunschweig, Stefan Lueders, Konstantinos Tsaknakis, Heiko M. Lorenz, Anna K. Hell
Summary: Magnetic resonance imaging showed that scoliotic children experienced a reduction in intervertebral disc volume and degeneration after long-term treatment with magnetically controlled growing rods. Compared to untreated children, those who underwent treatment showed more intervertebral disc degeneration.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Biotechnology & Applied Microbiology
Jintao Liu, Pengfei Yu, Feng Dai, Hong Jiang, Zhijia Ma
Summary: This study focused on exploring whether Tetrandrine (TET) attenuated tert butyl hydrogen peroxide (TBHP)-induced nucleus pulposus (NP) cell injury and delayed rat intervertebral disc degeneration (IDD) by inducing autophagy. TET reversed the effect of TBHP on NP cells, enhancing autophagy and reducing oxidative stress, apoptosis, and extracellular matrix (ECM) degradation. In vivo, TET delayed rat IDD, increased the expression of LC3 and collagen II, and weakened apoptosis. TET may be a potential candidate drug for the treatment of IDD.
Article
Cell & Tissue Engineering
Sebastian Wangler, Amir Kamali, Christina Wapp, Karin Wuertz-Kozak, Sonja Haeckel, Claudia Fortes, Lorin M. Benneker, Lisbet Haglund, R. Geoff Richards, Mauro Alini, Marianna Peroglio, Sibylle Grad
Summary: MSC’s secretome composition was analyzed after exposure to different IVD environments, showing more complex secretome induced by IVD conditioned media compared to IL-1 beta stimulation. The secretome reflected different activity based on IVD pathological status, with implications for tailored secretome therapy development.
STEM CELL RESEARCH & THERAPY
(2021)
Article
Endocrinology & Metabolism
Archana Kamalakar, Jay M. McKinney, Daniel Salinas Duron, Angelica M. Amanso, Samir A. Ballestas, Hicham Drissi, Nick J. Willett, Pallavi Bhattaram, Andres J. Garcia, Levi B. Wood, Steven L. Goudy
Summary: This research indicates that exogenous delivery of JAG1 using synthetic hydrogels can promote robust bone regeneration in mice. JAG1 induces osteoblast proliferation through non-canonical genes, independent of the NOTCH canonical pathway. Pathway analysis reveals upregulation of multiple non-canonical pathways related to osteogenesis with JAG1 delivery, suggesting its translational potential as a bone-regenerative approach.
Article
Biochemistry & Molecular Biology
Angelica Mastandrea Amanso, Archana Kamalakar, Sara Bitarafan, Shelly Abramowicz, Hicham Drissi, Joey Victor Barnett, Levi Benjamin Wood, S. L. Goudy
Summary: Our study demonstrates the crucial role of TGF beta receptor 3 in inducing mineralization in bone cells through noncanonical targets of TGF beta signaling. Treatment with soluble TGF beta R3 increased mineralization in human pediatric bone-derived osteoblast-like cells, showing potential for bone inductive therapy. Further research will focus on utilizing sR3 to induce bone regeneration in vivo using animal models.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2021)
Article
Endocrinology & Metabolism
Se Hwan Mun, Sandra Jastrzebski, Judy Kalinowski, Steven Zeng, Brian Oh, Seyeon Bae, Giannopoulou Eugenia, Nazir M. Khan, Hicham Drissi, Ping Zhou, Bongjin Shin, Sun-Kyeong Lee, Joseph Lorenzo, Kyung-Hyun Park-Min
Summary: Sexual dimorphism plays a significant role in osteoclast formation, with females showing greater numbers of osteoclasts and accelerated differentiation compared to males. Gene expression profiling revealed 125 genes that are differentially regulated in a sex-dependent manner, impacting pathways related to innate immune and inflammatory responses. The NF-kappa B-NFATc1 axis is activated earlier in female osteoclast precursor cells, contributing to transcriptomic sexual dimorphism.
JOURNAL OF BONE AND MINERAL RESEARCH
(2021)
Article
Endocrinology & Metabolism
John Garcia, Spenser S. Smith, Sangita Karki, Hicham Drissi, Henry H. Hrdlicka, Daniel W. Youngstrom, Anne M. Delany
Summary: miR-433-3p is a negative regulator of bone formation through various key signaling pathways such as PTH, MAPK, Wnt, and endogenous glucocorticoids, targeting multiple genes including Crebl, Hsd11b1, and Rspo3 to inhibit osteoblast activity and Wnt signaling pathway, reducing bone mass. In in vivo experiments, inhibitors of miR-433-3p can increase trabecular bone volume in mice, indicating its negative regulatory role in bone formation.
JOURNAL OF BONE AND MINERAL RESEARCH
(2021)
Article
Orthopedics
Daniel Sok, Sarvgna Raval, Jay McKinney, Hicham Drissi, Amadeus Mason, Ken Mautner, Jarred M. Kaiser, Nick J. Willett
Summary: This study investigated the effects of pre- and post-treatment use of nonsteroidal anti-inflammatory drugs (NSAIDs) on the therapeutic efficacy of human mesenchymal stromal cell (hMSC) therapy for posttraumatic osteoarthritis (PTOA). The study found that pre-treatment with NSAIDs had minimal effects on therapeutic benefits, while post-treatment use of NSAIDs substantially reduced the efficacy of cellular treatment.
AMERICAN JOURNAL OF SPORTS MEDICINE
(2022)
Article
Immunology
Kyle Jones, Sergio Ramirez-Perez, Sean Niu, Umesh Gangishetti, Hicham Drissi, Pallavi Bhattaram
Summary: The study demonstrates the role of SOX4 and RELA in the regulation of gene expression downstream of TNF signaling, particularly in the transformation of FLS in arthritis and inflammatory pathology.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Endocrinology & Metabolism
Martha Elena Diaz-Hernandez, Christopher W. Kinter, Shana R. Watson, Giovanni Mella-Velazquez, Jarred Kaiser, Guanglu Liu, Nazir M. Khan, Joseph L. Roberts, Joseph Lorenzo, Hicham Drissi
Summary: This study explores the effects of Runx1, a transcription factor, on bone resorption and osteoclastogenesis. The researchers found that Runx1 acts as an inhibitor of osteoclast formation and its overexpression delays osteoclastogenesis and decreases bone resorption in a sex-dependent manner. Transcriptomics analysis revealed that Runx1 overexpression leads to a distinct gene expression profile related to redox signaling, apoptosis, osteoclast differentiation, and bone remodeling.
Article
Orthopedics
Changli Zhang, Katherine M. Joseph, Nazir M. Khan, Martha Elena Diaz-Hernandez, Hicham Drissi, Svenja Illien-Junger
Summary: The deficiency of PHLPP1 protects against age-related intervertebral disc (IVD) degeneration by preventing NP phenotypic changes, extracellular matrix degradation, and cell apoptosis, possibly through the activation of FOXO1.
Article
Biology
Nazir M. Khan, Martha Elena Diaz-Hernandez, Samir Chihab, Priyanka Priyadarshani, Pallavi Bhattaram, Luke J. Mortensen, Rosa M. Guzzo, Hicham Drissi
Summary: Induced pluripotent stem cells (iPSCs) have the potential to be used in regenerative medicine. iPSCs derived from healthy chondrocytes showed enhanced chondrogenic potential compared to iPSCs derived from osteoarthritis cartilage. The molecular tracing data revealed that epigenetic and metabolic factors dysregulation observed in osteoarthritis chondrocytes persisted in iPSCs, leading to their reduced chondrogenic differentiation.
Article
Biology
Sreedhara Sangadala, Chi Heon Kim, Lorenzo M. Fernandes, Pooja Makkar, George R. Beck, Scott D. Boden, Hicham Drissi, Steven M. Presciutti
Summary: This study identified three drugs that can disrupt the interaction between sclerostin and its receptor, LRP5/6, and promote bone fusion. These drugs enhance Wnt signaling and BMP signaling, induce mineralization, and generate new bone in vivo. They have the potential to be used as bone graft substitutes for spinal fusion and fracture healing.
Article
Geriatrics & Gerontology
Joseph L. Roberts, Brandon Chiedo, Hicham Drissi
Summary: Age is a crucial factor affecting fracture healing, as aging exacerbates the inflammatory response and disrupts the intestinal microbiota.
Article
Nanoscience & Nanotechnology
Daisy M. Ramos, Sama Abdulmalik, Michael R. Arul, Naseem Sardashti, Yeshavanth Kumar Banasavadi-Siddegowda, Syam P. Nukavarapu, Hicham Drissi, Sangamesh G. Kumbar
Summary: Approximately half of musculoskeletal injuries in the US involve tendon tears. Tendon injuries are common and slow to heal due to the nature of tendon tissue. Insulin-functionalized nanofiber matrices have been found to enhance tendon repair when combined with mesenchymal stem cells. The matrices promote collagen synthesis and alignment, contributing to functional recovery of the tendon.
ACS APPLIED BIO MATERIALS
(2022)
Article
Biochemistry & Molecular Biology
Chi Heon Kim, Colleen Oliver, Hamid Dar, Hicham Drissi, Steven M. Presciutti
Summary: Intervertebral disc degeneration is a major cause of low back pain worldwide. In this study, the researchers investigated the use of adenoassociated virus (AAV) as a tool for gene transfer in the intervertebral disc. They compared different AAV serotypes and parameters, and found that AAV6 with a CAG promoter at a titer of 1011 GC/mL achieved high transduction efficiency and low toxicity in murine nucleus pulposus cells. They also demonstrated the use of small cell permeabilization peptides to boost transduction efficiency, and utilized optical tissue clearing and three-dimensional lightsheet microscopy to visualize tissue and cell architecture after AAV6 delivery.
Article
Endocrinology & Metabolism
Joseph L. Roberts, Giovanni Mella-Velazquez, Hamid Y. Dar, Guanglu Liu, Hicham Drissi
Summary: This study suggests that IL-17ra signaling in preosteoclasts can contribute to osteoclast formation and subsequent bone loss. The deletion of IL-17ra in osteoclast precursors may lead to increased trabecular bone microarchitecture and decreased osteoclast number.
Article
Orthopedics
John Rodriguez-Feo, Lorenzo Fernandes, Anuj Patel, Thanh Doan, Scott D. Boden, Hicham Drissi, Steven M. Presciutti
Summary: The study investigated the spatial and temporal expression patterns of Wnt signaling factors and inhibitors during spinal fusion, revealing distinct differences and potentially aiding in the development of novel biologics to increase spinal fusion rates.