In Vitro and In Vivo Bone-Forming Effect of a Low-Molecular-Weight Collagen Peptide

Abstract

deteriorates. Bone degradation can be delayed through the activation of bone generation or the obstructing of bone resorption. Several drugs can regulate the bone remodeling process, including bisphosphonates, selective estrogen receptor modulators, parathyroid hormone, and sclerostin [2]. However, these treatments have safety issues or are characterized by serious side effects (such as increased micro-fracture accumulations, infections, stroke or cardiovascular events) [3]. Thus, it is crucial to develop safer treatments that can facilitate bone formation.Collagen is a crucial constituent of the skin, cartilage, tendons, and bones. Its function is to maintain their functionality and structure. Collagen is the main component of the extracellular matrix (ECM), which is linked to important cellular processes such as the regulation of cell adhesion and proliferation, the regulation of growth factors ' effectiveness, and differentiation [4]. The deposition of collagen can lead to ECM synthesis and bone reinforcement stimulation.Through an enzyme-mediated reaction, collagen produces collagen hydrolysate or collagen peptides [5]. Collagen hydrolysate can exert various beneficial effects, including antiaging, antiobesity, and wound healing effects [6]. Clinical data have also revealed a positive effect of collagen hydrolysate on osteoporosis or bone formation [7,8]. In these studies, collagen hydrolysate was shown to improve the hematological factors related to bone remodeling and increase the levels of BMD in humans. Collagen tripeptide has also been shown to stimulate the healing of the fracture of the femur and tibia in vivo [9,10]. Moreover, Liu et al. have investigated the differentiating effect of hydrolyzed fish collagen on bone marrow mesenchymal stem cells [11], while the intake of hydrolyzed collagen [12] and cod gelatin [13] has been shown to increase the BMD of ovariectomized rats. We believe that collagen peptides, which are known to be safe to eat and have a low possibility of causing allergic reactions [14], could potentially stimulate the preosteoblastic cells and the microarchitecture of the femur and the lumbar vertebrae in ovariectomized rats.We have previously demonstrated wrinkle reduction as well as hydration and elasticity enhancement of the human skin because of the oral administration of a low-molecular-weight collagen peptide (LMWCP) containing Gly-Pro-Hyp at 3% w/w and collagen tripeptide at over 15% w/w [15]; these effects are mediated by the promotion of the synthesis of type I collagen and of hyaluronic acid in skin fibroblasts [16,17]. Moreover, our study revealed that orally consumed LMWCP can alleviate osteoarthritis progression in an anterior cruciate ligament transection This study reveals that low-molecular-weight collagen peptide (LMWCP) can stimulate the differentiation and the mineralization of MC3T3-E1 cells in vitro and attenuate the bone remodeling process in ovariectomized (OVX) Sprague-Dawley rats in vivo. Moreover, the assessed LMWCP increased the activity of alkaline phospha...