MSC Differentiation. Differentiation of MSCs into three mesenchymal cell lineages has been proposed as an important characteristic of MSCs and different studies have demonstrated their in vivo capacity to differentiate into osteoblasts (Xxxxxxxxxxxx, Xxxxxxxxxxx et al. 1970, Xxxxxxxx, Xxxxxxx et al. 1989), adipocytes (Xxxxxxxxx, Xxxxxxx et al. 1992) and chondrocytes (Xxxxxxxxx, Hering et al. 1998). Osteogenesis in MSCs Bone is a dynamic, multifunctional connective tissue, with high turnover. Bone formation and remodelling is a process beginning with mesenchymal progenitors which then undergo osteoblast lineage differentiation. After proliferation, these cells secret extracellular matrix which is then mineralised (Paic, Xxxx et al. 2009). The existence of skeletal progenitor cells in the bone marrow was first described by Xxxxxxxxxxxx et al, in 1976. They found that there are mechanocyte precursor clones, among clonogenic cells of connective tissue cultured in vitro with a lower renewal rate than hemopoietic cells, which retain differentiation features characteristic of the source tissue when expanded (Xxxxxxxxxxxx 1976). Bone formation There are two different processes which result in ossification. One is endochondral ossification that occurs in cartilage template and forms long bone and the other one is intramembranous ossification which initiates by condensation of mesenchymal cells, transforming to osteoblasts at the centre of ossification. This process happens during flat bone formation (Xx, Xxxxx et al. 1997). Bone matrix consists of different proteins in which collagen type I is the most abundant and makes up almost 90% of organic bone matrix. The other non-collagenous proteins include osteocalcin (bone GLA protein) osteopontin, osteonectin and bone sialoprotein which in addition to proteoglycans and biglycan form the organic matrix (Xxxxxx, Xxxxxx et al. 2006). Collagen type I belongs to the collagen superfamily and is the main component to maintain mechanical strength, structure and elasticity of bone. Also, it acts as a matrix deposition template during mineralisation (Uitto and Xxxxx 2000). Bone sialoprotein (BSP), is a major non-collagenous extracellular matrix protein in bone, which is secreted by osteoclasts, osteoblasts, osteocytes, and hypertrophic chondrocytes (Xxxxxx, Xxxxxx et al. 1996) (Reviewed by (Xxxxx 2003)). Osteopontin (OPN), also known as bone sialoprotein I (BSP1) and secreted phosphoprotein I (SPP1), is a non-collagenous protein produced by osteobla...
