ABSTRACT
IL-3 is an important cytokine that regulates hematopoiesis. We have previously demonstrated that IL-3 is a potent inhibitor of osteoclastogenesis and bone resorption. In the present study, we have investigated the role of IL-3 on human osteoblast differentiation and bone formation. We found that IL-3 in a dose-dependent manner increases osteoblast differentiation and matrix mineralization in human mesenchymal stem cells (MSCs). IL-3 significantly enhances the expression of osteoblast specific genes such as alkaline phosphatase, collagen type-I, osteocalcin and osteopontin; and Runx-2 and osterix transcription factors. Moreover, IL-3 induces the expression of bone morphogenetic protein-2 (BMP-2), and activates smad1/5/8. IL-3 enhances osteoblast differentiation and BMP-2 secretion through JAK/STAT pathway. Interestingly, IL-3 promotes in vivo bone regeneration ability of MSCs. Thus, we reveal for the first time that IL-3 enhances human osteoblast differentiation and bone formation in both in vitro and in vivo conditions, and suggest its therapeutic potential for bone formation in important bone diseases.
Subject(s)
Cell Differentiation , Interleukin-3/physiology , Mesenchymal Stem Cells/cytology , Osteoblasts/cytology , Osteogenesis , Alkaline Phosphatase/biosynthesis , Animals , Bone Morphogenetic Protein 2/biosynthesis , Bone Regeneration , Collagen Type I/biosynthesis , Core Binding Factor Alpha 1 Subunit/biosynthesis , Humans , Interleukin-3/pharmacology , Interleukin-3 Receptor alpha Subunit/biosynthesis , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Mice , Mice, Inbred BALB C , Mice, SCID , Osteocalcin/biosynthesis , Osteopontin/biosynthesis , Sp7 Transcription Factor , Transcription Factors/biosynthesisABSTRACT
Vaccines currently available across the globe are stored and transported in a continuous cold-chain at 2-8°C or below -20°C. A temperature excursion outside this range affects the potency of the vaccines. Such vaccines need to be discarded leading wastage. The Rotavirus disease burden is predominantly reported in developing and low-income countries and therefore, has entered or poised to enter their national immunization programs. These countries already have several limitations for effective storage, maintenance and distribution of vaccines in a cold-chain and this introduction is expected to further stress this fragile ecosystem. To help mitigate the cold chain related issues, SIIPL has developed a thermostable rotavirus vaccine ROTASIIL® which can be stored at a temperature below 25°C for 36months, completely by-passing the standard 2-8°C cold storages. In addition it has the capability to withstand temperatures of 37°C and 40°C for 18months and short term exposure to 55°C. It can also tolerate a temperature shock of being thawed from an extreme cold temperature of -20°C to a high temperature of 42°C. The vaccine contains serotypes G1, G2, G3, G4 and G9 (UK-Bovine reassortant strains procured from National Institute of Health-USA). The vaccine is recently licensed in India.
Subject(s)
Hot Temperature , Rotavirus Vaccines/chemistry , Vaccine Potency , Animals , Cattle , Drug Stability , Drug Storage , Freeze Drying , Humans , India , Refrigeration , Rotavirus/classification , Rotavirus/immunology , Rotavirus Infections/prevention & control , Serogroup , Time Factors , Vaccines, Attenuated/chemistryABSTRACT
A bovine rotavirus pentavalent vaccine (BRV-PV) containing rotavirus human-bovine (UK) reassortant strains of serotype G1, G2, G3, G4 and G9 has been developed by the Serum Institute of India Ltd, in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID), USA. The vaccine underwent animal toxicity studies and Phase I and II studies in adults, toddlers and infants. It has been found safe and immunogenic and will undergo a large Phase III study to assess efficacy against severe rotavirus gastroenteritis.