Rosemary Extract-Induced Autophagy and Decrease in Accumulation of Collagen Type I in Osteogenesis Imperfecta Skin Fibroblasts

Abstract

Osteogenesis imperfecta (OI) is a heterogeneous connective tissue disease mainly caused by structural mutations in type I collagen. Mutant collagen accumulates intracellularly, causing cellular stress that has recently been shown to be phenotype-related. Therefore, the aim of the study was to search for potential drugs reducing collagen accumulation and improving OI fibroblast homeostasis. We found that rosemary extract (RE), which is of great interest to researchers due to its high therapeutic potential, at concentrations of 50 and 100 µg/mL significantly reduced the level of accumulated collagen in the fibroblasts of four patients with severe and lethal OI. The decrease in collagen accumulation was associated with RE-induced autophagy as was evidenced by an increase in the LC3-II/LC3-I ratio, a decrease in p62, and co-localization of type I collagen with LC3-II and LAMP2A by confocal microscopy. The unfolded protein response, activated in three of the four tested cells, and the level of pro-apoptotic markers (Bax, CHOP and cleaved caspase 3) were attenuated by RE. In addition, the role of RE-modulated proteasome in the degradation of unfolded procollagen chains was investigated. This study provides new insight into the beneficial effects of RE that may have some implications in OI therapy targeting cellular stress.

Beneficial Effects of Zoledronic Acid on Tendons of the Osteogenesis Imperfecta Mouse (Oim)

“…In OI mouse models, an accumulation of mutated type I collagen in the endoplasmic reticulum of osteoblasts induces stress and may be related to the clinical outcome [45]. A recent study also highlighted this phenomenon in skin fibroblasts [46]. It would be interesting to investigate this phenomenon on tenocytes, and to study a possible effect of mechanical stimulation on this cellular stress.…”

Anticancer Effects of Rosmarinus officinalis Leaf Extract on KB Cell Lines

“…Because the rosemary plant contains secondary metabolites like diterpenoids and polyphenols, which have anti-oxidative properties, traditional medicine practices like Ayurveda also use rosemary extracts [ 9 ]. Rosemary extract protects against the oral administration of croton oil, which works as a promoter, and 7, 12 dimethylbenzanthracene, which functions as an initiator to cause skin cancer in mice [ 10 ]. The spasmolytic activity of rosemary essential oil, which relaxes the muscles and reduces spasms, makes it special [ 11 ].…”

Health Properties of Plant Bioactive Compounds: Immune, Antioxidant, and Metabolic Effects

“…The clinical application of a vegetable extract of Rosmarinus officinalis (rosemary) was studied in four patients with osteogenesis imperfecta, a genetic connective tissue disease [11]. In this study, the extract reduced collagen accumulation in the fibroblasts of patients, due to increased autophagy of fibroblasts.…”