Sericin’s Potential in Osteoporosis Management: The Roles of L-Serine and D-Serine in Bone Metabolism Regulation

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Background: Osteoporosis is a bone remodeling disease characterized by an imbalance between bone formation and resorption, leading to bone fragility. Current treatments focus on bone resorption suppression but often have adverse effects. This study aimed to explore the potential of sericin, a silkworm-derived protein, as a dual-action therapeutic agent that enhances bone formation through its component L-serine and inhibits bone resorption via D-serine, which is derived from L-serine by the action of serine racemase. Methods: Cellular experiments were conducted to evaluate the effects of L-serine on osteoblast differentiation and D-serine on osteoclast inhibition. Serum levels of D-serine were measured following sericin administration in an osteoporosis animal model. μ-CT analysis assessed trabecular and cortical bone quality, and bone-related protein expression was analyzed using immunoprecipitation-based high-performance liquid chromatography (IP-HPLC). Results: L-serine significantly upregulated osteogenic markers, including alkaline phosphatase (ALP), Runx2, osterix, and Col1a1, in osteoblasts (p < 0.05). D-serine inhibited osteoclast activation by suppressing cathepsin K expression (p < 0.001). Sericin feeding elevated serum D-serine levels (p < 0.001) and upregulated bone-related proteins such as BMP-2, osterix, and Runx2. Micro-computed tomography (μ-CT) analysis revealed significant improvements in trabecular bone parameters in the OVX-sericin group, including increased trabecular bone volume (Tb.BV/TV; p < 0.05) and reduced trabecular separation (Tb.Sp; p < 0.05), compared to the OVX and OVX-amino acid groups. Cortical bone parameters, including cortical bone volume (Ct.BV/TV) and cortical area (Ct.Ar), did not significantly differ among OVX groups, but all were lower than in the sham group (p < 0.05). Conclusions: This study demonstrates that sericin modulates bone metabolism by enhancing osteoblast activity through L-serine and inhibiting osteoclastogenesis via D-serine. Sericin supplementation improved trabecular bone mass in an osteoporosis model, highlighting its potential for bone health.