Details

Autor(en) / Beteiligte

• Carvalho, Marta S.
• Silva, João C.
• Hoff, Christopher M.
• Cabral, Joaquim M. S.
• Linhardt, Robert J.
• Silva, Cláudia L.
• Vashishth, Deepak

Titel

Loss and rescue of osteocalcin and osteopontin modulate osteogenic and angiogenic features of mesenchymal stem/stromal cells

Ist Teil von

• Journal of cellular physiology, 2020-10, Vol.235 (10), p.7496-7515

Ort / Verlag

United States: Wiley Subscription Services, Inc

Erscheinungsjahr

2020

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• Noncollagenous proteins in the bone extracellular matrix, such as osteocalcin (OC) and osteopontin (OPN), inherent to evolution of bone as a skeletal tissue, are known to regulate bone formation and mineralization. However, the fundamental basis of this regulatory role remains unknown. Here, for the first time, we use mouse mesenchymal stem/stromal cells (MSC) lacking both OC and OPN to investigate the mechanistic roles of OC and OPN on the proliferation capacity and differentiation ability of MSC. We found that the loss of OC and OPN reduces stem cells self‐renewal potential and multipotency, affects their differentiation into an osteogenic lineage, and impairs their angiogenic potential while maintaining chondrogenic and adipogenic lineages. Moreover, loss of OC and OPN compromises the extracellular matrix integrity and maturation, observed by an unexpected enhancement of glycosaminoglycans content that are associated with a more primitive skeletal connective tissue, and by a delay on the maturation of mineral species produced. Interestingly, exogenously supplemented OC and OPN were able to rescue MSC proliferative and osteogenic potential along with matrix integrity and mineral quality. Taken together, these results highlight the key contributions of OC and OPN in enhancing osteogenesis and angiogenesis over primitive connective tissue, and support a potential therapeutic approach based on their exogenous supplementation. Here, for the first time, we use mesenchymal stem/stromal cells (MSC) lacking both osteocalcin (OC) and osteopontin (OPN) to investigate the mechanistic roles of OC and OPN on the proliferation capacity and differentiation ability of MSC. We found that the loss of OC and OPN reduces stem cells' self‐renewal potential and multipotency, affects their differentiation into an osteogenic lineage, and impairs their angiogenic potential while compromising the extracellular matrix integrity and maturation. Taken together, these results highlight the key contributions of OC and OPN in enhancing osteogenesis and angiogenesis over primitive connective tissue, and support a potential therapeutic approach based on their exogenous supplementation.