Collagen I and collagen III expression in fibrotic bone marrow

Shehata, A.; Kandel, Samia H; Rizk, Samia; Khalifa, Khalid Al; Fouad, Ahmad

doi:10.4103/1110-2098.192403

Cited by 2 publications

(3 citation statements)

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“…These results agree with the pathomolecular mechanism of MC, in particular MC1, where bone marrow fibrosis has been described [2,10]. Type III and IV collagen are key bone marrow matrix constituents and known to be increased in bone marrow fibrosis [36]. From biomarker studies of other fibrotic diseases, including myelofibrosis, it is likely that an increase of PRO-C3 correlates with an increased type III collagen deposition.…”

Section: Discussionsupporting

confidence: 86%

“…The biomarkers PRO-C3, PRO-C4, C3M, and C4M that correlate with MC have been identified as markers for other fibrotic conditions. In myelofibrosis, a myeloproliferative and fibrotic disease of the bone marrow, serum PRO-C3 and PRO-C4 have already been described as potential biomarkers that correlate with increased type III and IV collagen in the bone marrow [36][37][38][39][40]. PRO-C4 has been identified as a serum marker to predict the progression of systemic sclerosis [41].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, resorption of the disc generates neo-epitopes of type I and II collagen and aggrecan. In myelofibrosis (a fibrotic condition of the bone marrow different from MC), type I and III collagen are the major deposited matrix constituents [36]. Neovascularization of fibrotic bone marrow increases the spatial abundance of type IV collagen because type IV collagen is the main constituent of the basement membrane of vascular sinusoids [37,38].…”

Section: Introductionmentioning

confidence: 99%

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Serum Biomarkers for Connective Tissue and Basement Membrane Remodeling Are Associated with Vertebral Endplate Bone Marrow Lesions as Seen on MRI (Modic Changes)

Dudli

Ballatori

Bay‐Jensen

et al. 2020

IJMS

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Vertebral endplate bone marrow lesions, visualized on magnetic resonance imaging (MRI) as Modic changes (MC), are associated with chronic low back pain (cLBP). Since guidelines recommend against routine spinal MRI for cLBP in primary care, MC may be underdiagnosed. Serum biomarkers for MC would allow early diagnosis, inform clinical care decisions, and supplement treatment monitoring. We aimed to discover biomarkers in the blood serum that correlate with MC pathophysiological processes. For this single-site cross-sectional study, we recruited 54 subjects with 38 cLBP patients and 16 volunteers without a history of LBP. All subjects completed an Oswestry Disability Index (ODI) questionnaire and 10-cm Visual Analog Score (VAS) for LBP (VASback) and leg pain. Lumbar T1-weighted and fat-saturated T2-weighted MRI were acquired at 3T and used for MC classification in each endplate. Blood serum was collected on the day of MRI. Biomarkers related to disc resorption and bone marrow fibrosis were analyzed with enzyme-linked immune-absorbent assays. The concentration of biomarkers between no MC and any type of MC (AnyMC), MC1, and MC2 were compared. The Area Under the Curve (AUC) of the Receiver Operating Characteristics were calculated for each biomarker and for bivariable biomarker models. We found that biomarkers related to type III and type IV collagen degradation and formation tended to correlate with the presence of MC (p = 0.060–0.088). The bivariable model with the highest AUC was PRO-C3 + C4M and had a moderate diagnostic value for AnyMC in cLBP patients (AUC = 0.73, specificity = 78.9%, sensitivity = 73.7%). In conclusion, serum biomarkers related to the formation and degradation of type III and type IV collagen, which are key molecules in bone marrow fibrosis, correlated with MC presence. Bone marrow fibrosis may be an important pathophysiological process in MC that should be targeted in larger biomarker and treatment studies.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Serum Biomarkers for Connective Tissue and Basement Membrane Remodeling Are Associated with Vertebral Endplate Bone Marrow Lesions as Seen on MRI (Modic Changes)

Dudli

Ballatori

Bay‐Jensen

et al. 2020

IJMS

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Exposure of Patient-Derived Mesenchymal Stromal Cells to TGFB1 Supports Fibrosis Induction in a Pediatric Acute Megakaryoblastic Leukemia Model

Hack

Bertram

Blair

et al. 2020

Molecular Cancer Research

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Bone marrow fibrosis (BMF) is a rare complication in acute leukemia. In pediatrics, it predominantly occurs in acute megakaryoblastic leukemia (AMKL) and especially in patients with trisomy 21, called myeloid leukemia in Down syndrome (ML-DS). Defects in mesenchymal stromal cells (MSC) and cytokines specifically released by the myeloid blasts are thought to be the main drivers of fibrosis in the bone marrow niche (BMN). To model the BMN of pediatric patients with AMKL in mice, we first established MSCs from pediatric patients with AMKL (n ¼ 5) and ML-DS (n ¼ 9). Healthy donor control MSCs (n ¼ 6) were generated from unaffected children and adolescents ≤18 years of age. Steady-state analyses of the MSCs revealed that patient-derived MSCs exhibited decreased adipogenic differentiation potential and enrichment of proliferation-associated genes. Importantly, TGFB1 exposure in vitro promoted early profibrotic changes in all three MSC entities. To study BMF induction for longer periods of time, we created an in vivo humanized artificial BMN subcutaneously in immunodeficient NOD.Cg-Prkdc scid Il2rg tm1Wjl /SzJ mice, using a mixture of MSCs, human umbilical vein endothelial cell, and Matrigel. Injection of AMKL blasts as producers of TGFB1 into this BMN after 8 weeks induced fibrosis grade I/II in a dose-dependent fashion over a time period of 4 weeks. Thus, our study developed a humanized mouse model that will be instrumental to specifically examine leukemogenesis and therapeutic targets for AMKL blasts in future.Implications: TGFB1 supports fibrosis induction in a pediatric AMKL model generated with patient-derived MSCs.

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Collagen I and collagen III expression in fibrotic bone marrow

Cited by 2 publications

References 0 publications

Serum Biomarkers for Connective Tissue and Basement Membrane Remodeling Are Associated with Vertebral Endplate Bone Marrow Lesions as Seen on MRI (Modic Changes)

Serum Biomarkers for Connective Tissue and Basement Membrane Remodeling Are Associated with Vertebral Endplate Bone Marrow Lesions as Seen on MRI (Modic Changes)

Exposure of Patient-Derived Mesenchymal Stromal Cells to TGFB1 Supports Fibrosis Induction in a Pediatric Acute Megakaryoblastic Leukemia Model

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