Osteosarcoma: From Molecular Biology to Mesenchymal Stem Cells

Abstract

Osteosarcoma is the most common primary malignant tumour of bone. Currently, despite treatment with multi-agent chemotherapy and limb salvage surgery, the iveyear survival rate for osteosarcoma remains at 70%. The pathogenesis of osteosarcoma is complex and involves alterations in cellular apoptosis, adhesion, migration, invasion and molecular signalling. Research most recently has focused on the molecular basis of the disease with the goal of identifying novel therapeutic targets. To this end, mesenchymal stem cells (MSCs) have been identiied to play a role in sarcomagenesis. MSC transformation may give rise to tumours, whereas interactions of MSCs with osteosarcoma cells in the tumour microenvironment may cause increased cell proliferation. This is in stark contrast to the role of MSCs as a promising source for tissue repair and regeneration. In order to utilize MSCs for biological reconstruction in the seting of osteosarcoma, further research is necessary to delineate the role of MSCs in osteosarcoma transformation and progression.

Pathogenesis and Current Treatment of Osteosarcoma: Perspectives for Future Therapies

“…These cells control the formation of osteoblasts and bone matrix and recruit hematopoietic cells to incorporate blood vessels. Transforming growth factor-beta (TGFβ) expression can further drive differentiation into chondrocytes, but also stimulates alkaline phosphatase (ALP) activity and calcium deposition [ 1 , 7 ].…”

“…Importantly, p27KIP1 is lost in differentiated osteosarcoma, driving cell cycle exit and normal bone development upon Runx2-mediated activation [ 6 ]. ALP, another factor elevated by Runx2, is required for the differentiation of mesenchymal stem cells to osteoblasts, but decreases as normal differentiation continues [ 1 ]. Enhanced serum ALP levels have been identified in osteosarcoma patients, indicating a role in osteosarcomagenesis [ 30 , 31 ].…”

“…Osteosarcoma arising in Paget’s disease patients have been found to have a higher incidence of p53 mutation, as well as mutations to other tumor suppressor genes, suggesting that a second “hit” is required for osteosarcomagenesis in patients with Paget’s disease [ 51 ]. Other diseases, including Bloom syndrome (driven by a mutation to the BLM gene), Werner syndrome ( WRN gene mutation), and Rothman-Thompson syndrome ( RECQL4 gene mutation), have also been correlated with increased osteosarcoma incidence [ 1 , 6 , 52 ].…”

“…Osteosarcomas are the most common pediatric and adult bone tumor, with more than 1000 new cases every year in the United States alone. Osteosarcomas arise from mesenchymal cells and are characterized by areas of abnormal bone growth [ 1 ]. The various genetic, epigenetic, and environmental factors that drive mesenchymal stem cells to differentiate into bone precursor cells also play a role in the development of osteosarcoma.…”

Exosome-Functionalized, Drug-Laden Bone Substitute along with an Antioxidant Herbal Membrane for Bone and Periosteum Regeneration in Bone Sarcoma

“…The clinical management of large bone defects resulting from musculoskeletal tumors, bone infections, and trauma leads to a tissue devoid of blood supply (due to periosteum loss) and functionally inferior to regenerate the lost bone . Bone tumor or osteosarcoma (OS) affects the equilibrium of osteogenesis and is characterized by the formation of immature bone by growing cells with an incidence rate of 3 people/million/year. , The course of treatment entails surgical resection with pre- or postoperative chemotherapy using a systemic high dose of an established anti-cancer medication like doxorubicin. The systemic distribution of medications causes side effects such as damage to mucosal tissue, hair loss, heart illnesses, etc.…”