Using a specific antibody to block integrin alpha2beta1, Mk adhesion to hOSTs was reduced, but their ability to extend propletelets was restored, eliminating the inhibitory effect induced by the binding of released type I collagen to its adhesive receptor on the Mk membrane. Previous work found that the inhibitory action of type I collagen on PPF is dependent on myosin IIA, the only isoform expressed in Mks and platelets and is encoded by the MYH9 gene, whose mutations cause thrombocytopenia. Two recent reports have implicated myosin IIA in the Rho/ROCK-mediated inhibition of PPF. The results presented here support these previous findings of myosin-IIA as a key element in Mk regulation, demonstrating that inhibition of myosin IIA counteracts the ability of type I collagen to repress PPF in a physiological setting of the osteoblastic niche. Together, these results indicate that type I collagen can negatively control PPF as long as the functionality of myosin is preserved. Interestingly, previous work in the lab showed that megakaryocytes obtained from the peripheral blood of patients with specific MYH9 mutations present a loss of function of myosin-IIA and completely lose the physiologic suppression of PPF exerted by type I collagen. Finally, as it is known that hOSTs produce several cytokines that are critical for hemopoiesis and megakaryopoiesis, this work extends these observations by demonstrating that physical contact Norisoboldine between the osteoblastic niche environment and Mks can inhibit PPF that is otherwise enhanced when Procyanidin-B1 interactions between HSCs and their environment are missing. These results strongly support the conclusion that different elements combine to regulate Mk maturation within the osteoblastic niche and a perturbation of a single element can cause premature proplatelet extension and ineffective platelet release into the blood stream. Different cells, other than hOSTs, derive from hMSCs into the bone marrow and support megakaryopoiesis. Moreover, it has been shown that hMSCs stimulate Mk and platelet production from HSCs.