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Comparative Analysis of Serine Isomers and Sericin Sources in Promoting Osteoblastic Differentiation

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Bone regeneration remains a significant clinical challenge, particularly in osteoporotic conditions where impaired osteoblastic function compromises skeletal repair. Recently interest has focused on metabolic and biomaterial-based interventions to enhance osteogenesis. This study investigates the osteogenic potential of L-serine and D-serine—two metabolically active amino acid isomers—and compares the bioactivity of Sericin extracted from silkworm cocoons using a high-temperature (Sericin-K) and enzymatically hydrolyzed sericin (Sericin-C) in human bone marrow-derived mesenchymal stem cells (BMMSCs). BMMSCs were treated with varying concentrations of L-serine, D-serine, or sericin extracts and induced toward osteogenic differentiation. Mineralization was assessed by Alizarin Red S staining, and gene expression of osteogenic markers (Runx2, BMP2, Cx43, OPN, OPG) was quantified via qRT-PCR. L-serine promoted delayed but robust mineralization, with strong upregulation of late-stage markers such as OPN and OPG. In contrast, D-serine induced earlier mineral deposition, potentially through NMDA receptor-mediated signaling, but elicited a more modest transcriptional response. Sericin-K significantly outperformed Sericin-C enhance osteoblastic differentiation through distinct temporal and molecular mechanisms. Moreover, Sericin-K exhibits superior osteoinductive ability compared to Sericin-C. These findings support the therapeutic potential of combining amino acid-based metabolic modulation with region-specific biomaterials to improve bone regeneration outcomes.

Abstract

Bone regeneration remains a significant clinical challenge, particularly in osteoporotic conditions where impaired osteoblastic function compromises skeletal repair. Recently interest has focused on metabolic and biomaterial-based interventions to enhance osteogenesis. This study investigates the osteogenic potential of L-serine and D-serine—two metabolically active amino acid isomers—and compares the bioactivity of Sericin extracted from silkworm cocoons using a high-temperature (Sericin-K) and enzymatically hydrolyzed sericin (Sericin-C) in human bone marrow-derived mesenchymal stem cells (BMMSCs). BMMSCs were treated with varying concentrations of L-serine, D-serine, or sericin extracts and induced toward osteogenic differentiation. Mineralization was assessed by Alizarin Red S staining, and gene expression of osteogenic markers (Runx2, BMP2, Cx43, OPN, OPG) was quantified via qRT-PCR. L-serine promoted delayed but robust mineralization, with strong upregulation of late-stage markers such as OPN and OPG. In contrast, D-serine induced earlier mineral deposition, potentially through NMDA receptor-mediated signaling, but elicited a more modest transcriptional response. Sericin-K significantly outperformed Sericin-C enhance osteoblastic differentiation through distinct temporal and molecular mechanisms. Moreover, Sericin-K exhibits superior osteoinductive ability compared to Sericin-C. These findings support the therapeutic potential of combining amino acid-based metabolic modulation with region-specific biomaterials to improve bone regeneration outcomes.

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