Christian
A Roach
Effect of loss of hyaluronan synthases on glycosaminoglycan production in bone marrow derived cells STEM
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Authors:
Christian A Roach
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Osteoarthritis is a highly prevalent musculoskeletal disease with negative consequences such as swelling of the joint, joint pain, joint stiffness, and decreased range of motion. Although this disease can be extremely debilitating for affected individuals, no cure currently exists. One therapeutic target for the disease is modulating the endogenous production of hyaluronan. As osteoarthritis progresses, hyaluronan content declines. Hyaluronan is a glycosaminoglycan (GAG) that is produced by hyaluronan synthases (Has) 1, 2, and 3. In this work, we utilized Has1 knockout (-/-) and Has3 knockout (-/-) mice to evaluate contributions of Has1 and Has3 to matrix production. Sulfated glycosaminoglycans (sGAG) are a key component of the extracellular matrix (ECM) and as osteoarthritis progresses sGAG production declines. Bone marrow derived cells release sGAG that can remodel the ECM which can correlate to regeneration of damaged tissue. Bone marrow derived cells were isolated from Has1-/- and Has3-/- mice and cultured for 24 hours. This was followed by media collection. Dimethylmethylene blue assay was conducted to measure the sGAG content released from cells into the collected media. On average, bone marrow derived cells isolated from Has1-/- mice released 7.12 ug/mL sGAG into media while bone marrow derived cells isolated from Has3-/- mice released 7.60 ug/mL sGAG. Future work will involve the analysis of other matrix components such as hyaluronan. Understanding the relationship between hyaluronan synthases and GAG production can give us a better foundation for developing treatment options for osteoarthritis. Keywords: Glycosaminoglycan; Hyaluronan Synthase; Bone Marrow Stromal Cells
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Purdue University / 2025
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Christian A Roach