Osteogenic Activity of Collagen Peptide via ERK/MAPK Pathway Mediated Boosting of Collagen Synthesis and Its Therapeutic Efficacy in Osteoporotic Bone by Back-Scattered Electron Imaging and Microarchitecture Analysis

Abstract

Collagen hydrolysate (CH) has been reported to exhibit a positive effect on bone. In the present study, the in vitro effects of CH (<3 kDa) were examined and the in vivo experiments confirmed the positive effects of CH in ovariectomized (OVX) rats. Bone mineral density (BMD) was examined by DXA analysis. Scanning electron microscopic analysis and quantitative 3D-color backscattered electrons imaging analysis were performed on the lumbar vertebrae. CH increased osteoblastic cell proliferation and alkaline phosphatase activity in a dose-dependent manner. Collagen synthesis and collagen, type1, alpha1 (COL1A1) gene expression were also increased by CH treatment. Furthermore, CH-induced COL1A1 gene expression was completely abolished by extracellular signal-regulated kinase (ERK) inhibitor, suggesting the involvement of ERK/MAPK signaling for transcriptional effects on COL1A1 expression. OVX rats supplemented with CH showed osteoprotective effects as the BMD levels were increased compared with control. Moreover, CH prevented the trabecular bone loss induced by OVX and improved the microarchitecture of lumbar vertebrae. CH administration dose-dependently reduced the serum procollagen type I N-terminal propeptide level, which was elevated by OVX. The present study suggests that CH isolated in this study is a promising alternative to current therapeutic agents for the management of osteoporosis.

Collagen-derived dipeptide prolyl-hydroxyproline promotes differentiation of MC3T3-E1 osteoblastic cells

“…These results indicate that Pro-Hyp can promote the differentiation of osteoblasts by upregulating gene expression of Runx2 and Osterix. Previous reports have shown that treatment with crude CP increases the expression of the Runx2 and the Col1a1 genes in osteoblastic cells [13,14]. The regulation by Pro-Hyp in MC3T3-E1 cells would explain a mechanism of the protective effect of CP in bone metabolism.…”

“…Previous reports have shown that crude CP stimulates the proliferation of osteoblast cells. In one previous report, crude CP was used that may include various collagen-derived di-, tri-, and oligo-peptides such as Pro-Hyp, Pro-Hyp-Gly, Hyp-Gly, or Ala-Hyp [12][13][14]. It is speculated that these collagen-derived peptides, except Pro-Hyp, have the ability to enhance osteoblast proliferation.…”

“…Furthermore, some studies have indicated that crude CP has a beneficial effect on the proliferation or differentiation of osteoblastic cells [12][13][14]. Therefore, CP may also play an important role in bone remodeling.…”

The effect of different molecular weight collagen peptides on MC3T3-E1 cells differentiation

“…Collagens are peptide mixtures with different molecular weights. Hydrolyzed pigskin collagens smaller than 3,000Da are reported to prevent the bone loss due to ovariectomization, and improve microstructure of lumbar bones [18]. Oral medications of collagens smaller than 5,000Da can significantly increase the bone density and strength of ovariectomized rats.…”

Collagen supplementation as a complementary therapy for the prevention and treatment of osteoporosis and osteoarthritis: a systematic review

“…A study by Kim et al 28 considered bone loss to be a non-uniform process because the cancellous bone, the main component of the vertebrae, represents a higher risk than the cortical bone, the main component of the femur. Therefore, the lumbar vertebrae play a key role in monitoring OP.…”