Zn glycine attenuates LPS-induced inflammatory bone loss in geese through suppression of osteoclastogenesis via reducing TLR-4/NFκB signaling
Zeshan ZULFİQAR, Muhammad Arslan Asif, Layla Al-Mitib, Waseem Abbas, Xiaoyan Zhu, Aftab Shaukat, Zhichang Wang, Hao Sun, Yalei Cui, Boshuai Liu, Yinghua Shi
Abstract
Lipopolysaccharide (LPS), a major component of the outer membrane of gram-negative bacteria such as Escherichia coli, disrupts gut microbial homeostasis, compromises intestinal barrier integrity, and contributes to inflammation-associated bone loss. Although the gut-bone axis is increasingly recognized as a critical regulator of skeletal health, effective nutritional strategies targeting this pathway remain insufficiently explored. This study investigated the protective effects of Zn glycine, a highly bioavailable organic zinc chelates, against LPS-induced inflammatory bone loss in meat geese. Dietary supplementation with Zn glycine at 80 mg/kg significantly alleviated LPS-induced growth impairment, intestinal barrier dysfunction. Zn glycine markedly reduced LPS accumulation in both intestinal and bone tissues (p < 0.01) and enhanced tight junction integrity by upregulating zonula occludens-1 and claudin-1, thereby limiting systemic LPS translocation. These effects were accompanied by reduced pro-inflammatory cytokines (IL-1β, IL-18, and TNF-α), elevated anti-inflammatory cytokine IL-10, and increased microbial production of short-chain fatty acids, collectively supporting gut and bone health. Additionally, Zn glycine mitigated LPS-induced oxidative stress by enhancing antioxidant enzyme activities and total antioxidant capacity while reducing oxidative damage markers. Importantly, Zn glycine preserved bone microarchitecture, increased (p < 0.01) bone mineral density (BMD), suppressed osteoclastic genes such as tumor necrosis factor receptor-associated factor 6 (TRAF6) and nuclear factor of activated T-cells cytoplasmic 1 (NFATC1), and promoted osteoblast activity through upregulation of runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), and alkaline phosphatase (ALP). Mechanistically, these protective effects were mediated through inhibition of the TLR4/NF-κB signaling pathway. Overall, Zn glycine emerges as a promising nutritional strategy for preventing inflammation-driven bone loss via modulation of the gut-bone axis.