In conclusion our results demonstrate that CCLP promoted

In conclusion, our results demonstrate that CCLP promoted osteoblast proliferation, differentiation, and mineralization via activation of ERK, p38, and Smad1/5/8 (Fig. 9). The residues of the GGKQNVGFGP-sequence in CCLP showed the highest significant binding relationship with the target activin receptor. These findings provide a new insight into the effect of CCLP on osteoblast proliferation and differentiation and may eventually contribute to the treatment of bone diseases such as osteoporosis and management of bone repair by promoting bone formation.
Conflict of interest
Acknowledgment This research was supported by a grant from Marine Biotechnology Program (20150220) funded by Ministry of Oceans and Fisheries, Republic of Korea.
Introduction The first defense a pathogen, allergen, or environmental pollutant encounters when challenging the eye is the tear film. The tear film is produced in part by the conjunctiva which is a mucous membrane that functions as a part of the innate immune system of the eye, and provides a critical barrier between the ocular surface and the environment. The conjunctiva is comprised of stratified epithelial cells, a basement membrane and stroma. Within the epithelial layer of the conjunctiva are goblet cells. Conjunctival goblet Reserpine hydrochloride produce and secrete the high molecular weight glycoconjugate mucin MUC5AC, which protects the ocular surface by trapping pathogens, allergens, and environmental pollutants and removing them from the ocular surface by drainage through the nasolacrimal duct (Dartt and Masli, 2014; Jumblatt et al., 1999; Mantelli and Argueso, 2008). In uncontrolled inflammatory diseases like dry eye disease and allergic conjunctivitis, mucin secretion is dysregulated (Mantelli and Argueso, 2008; Govindarajan and Gipson, 2010; Contreras-Ruiz et al., 2013; McGilligan et al., 2013). Patients with dry eye disease usually have decreased tear film mucin and may suffer from burning, itching and blurred vision. Studies also show substantially decreased quality of life for these patients (Uchino and Schaumberg, 2013). Patients with allergic conjunctivitis have increased tear film mucins, but similarly to patients with dry eye, complain of symptoms including itching, redness and tearing. Vernal keratoconjunctivitis, a very severe form of allergic conjunctivitis, may even lead to vision loss (La Rosa et al., 2013). Dry eye disease and allergic conjunctivitis both have dysregulated tear film mucin production and both are growing public health problems for which current treatments are limited (Gayton, 2009; Gomes, 2014). Inflammation is crucial in order to remove pathogens, allergens, and environmental pollutants from the body. However, uncontrolled inflammation can occur without a pathogen, allergen, or tissue damage present, leading to unnecessary discomfort and tissue damage. In recent years, it has been established that there are lipid mediators which actively terminate the inflammation. These mediators are known as specialized pro-resolving mediators (SPMs) and consist of families termed resolvins, lipoxins, protectins and maresins (Serhan, 2014; Serhan and Chiang, 2013). The present study focuses on the SPM resolvin E1 (RvE1), which is produced from the omega-3 fatty acid eicosapentanoic acid (EPA) (Serhan et al., 2004). RvE1 induces intracellular signaling pathways through the ChemR23/ERV-1 receptor (Ohira et al., 2010). ChemR23 has been detected earlier by immunohistochemistry in rat conjunctival goblet cells (Dartt et al., 2011). Numerous studies show that RvE1 reduces inflammation in the eye. We demonstrated that RvE1 blocks the pro-inflammatory leukotriene (LT) D4-stimulated increase in goblet cell secretion from cultured rat conjunctival goblet cells (Dartt et al., 2011). In a murine model of dry eye disease, topical application of RvE1 decreased inflammatory markers and increased the number of goblet cells and tear production (Li et al., 2010; de Paiva et al., 2012). In other studies, RvE1 decreased inflammation in the cornea (Lee et al., 2015; Rajasagi et al., 2011; Jin et al., 2009). The long acting RvE1 analog RX-10045 reduced postoperative complications after laser refractive surgery (Torricelli et al., 2014). Furthermore, multiple studies indicate that a dietary intake of omega-3 fatty acids including EPA has a beneficial effect on dry eye disease (Miljanovic et al., 2005; Viau et al., 2009). To date, RvE1 has been used in one clinical trial where an analog of RvE1 reduced symptoms in dry eye disease patients (Serhan et al., 2014). Studies on a molecular level, in animal models and a clinical trial implicate a role for RvE1 in terminating ocular surface inflammation.