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Osteochondroprogenitor cells arise from Mesenchymal stem cells (MSC), which can be found in the bone marrow, and have the ability to differentiate into osteoblasts or chondrocytes depending on the signalling molecules they are exposed to. Osteochondroprogenitor cells are important for bone formation and maintenance.

Discovery
Alexander Friedenstein and his colleagues first identified osteoprogenitor cells in multiple mammalian tissues, before any genetic or morphological criteria were put in place for bone marrow or connective tissues. Osteoprogenitor cells can be identified by their associations with existing bone or cartilage structures, or their placement in the embryo, as the sites for osteogenesis and chondrogenesis are now known.

Cell Signalling and Differentiation
Osteochondroprogenitor can be found between MSCs and the terminally differentiated osteoblasts and chondrocytes. Via different signalling molecules and combinations the osteochondroprogenitor will differentiate into either osteoblasts or chondrocytes.

Differentiation into Chondrocytes
Main article: Chondrocytes

Chondrocytes are only present in cartilage where they will produce cartilaginous matrix to maintain the structure. Sox9, L-Sox5 and Sox6 are are needed for the osteochondroprogenitor to undergo chondrocytic differentiation. The transcription factor Sox9 can be found in multiple sites in the body (pancreas, central nervous system, intestines) and it is also found in all chondrocyte progenitor cells, suggesting that they are important in chondrogenesis.

Differentiation into Osteoblasts
Main article: Osteoblast

Osteoblasts are cells that group together to form units, called osteons, to produce bone. Runx2 (which may also be known as Cbfa1), and Osx (a zinc finger containing transcription factor) are necessary for osteochondroprogenitor cells to differentiate into the osteoblast cell lineage. These factors also have a role in hypertrophic chondrocyte maturation.

B-Catenin
Main article: Beta-catenin

B-catenin of the canonical Wnt signalling pathway plays a role in cell fate determination, as it is critical for osteoblastogenesis, and the differentiation of chondrocytes into osteoblasts. Knock out of the entire pathway results in early embryonic death, therefore most research of this nature utilised conditional knockouts of the pathway.

TGF-B
Main article: Transforming growth factor beta

During mandible development, most of it is formed through intramembranous ossification, where endochondral ossification will occur in the proximal region. TGF-B is important for cell proliferation and differentiation during skeletogenesis. During this process, TGF-B can stimulate differentiation into either chondrocytes or osteoblasts via FGF, Msx1, and Ctgf signalling pathways. General gene knock out of the TGF-B resulted in death. Conditional inactivation of TGF-Br2 of osteochondroprogenitor cells in the cranial neural crest resulted in faster osteoprogenitor differentiation and disorganised chondrogenesis.

TGF-B determines and regulates cell lineages during endochondral ossification, where it will act as a stimulator of chondrogenesis and an inhibitor of osteoblastic differentiation, by blocking the Runx2 factor through Smad3 activation. This is believed to be through the Sox9 and Runx2 factors. Sox9 stimulates differentiation into chondrocytes. In Sox9 blocked osteochondroprogenitor cells were found to express osteoblast marker genes, reprogramming the cells into the osteoblastic lineage.

Loss of TGF-B signalling will lead to reduced Sox9 activity, but not prevent it completely, leading to the belief that there must be other factors and signalling pathways regulating Sox9 activity. Once Sox9 activity is lost, differentiation into the osteoblastic lineage dominates.

Embryonic Development
It is thought that through a combination of biochemical and biophysical stimuli, the uncommitted stem cells of the embryo start to undergo differentiation into certain cell lineages. However the exact mechanism and signalling pathways are still unclear. However studies have shown that embryonic stem cells are more mechanosensitive than their differentiated counterparts. During embryonic development mesenchymal cells will form cellular structures known as ‘condensations.’ These cellular units will then develop into skeletal and other tissues, such as cartilage, tendon, ligament and muscle tissue.

Osteoprogenitor cell condensations can aggregate, dissipate or condense depending on the signals present, however these still remain largely unknown. Depending on the different effects, the cellular condensations may differentiate into osteogenic or chondrocytic condensations.

The positioning of the osteoprogenitor cell condensations determines the cell lineage before the signalling molecules can. This is due to their postions relative to any epithelial surfaces. Osteoblastic and chondrogenic condensations differ in their biophysical parameters within the embryo. Their distance in relation to the nearest epithelial surface will determine the cell lineage. For example osteoblastic condensations are closer to epithelial surfaces so they will be exposed to more biophysical and biochemical stimuli due to the proximity and increased cell-epithelial interactions.