The human skeleton is structurally unyielding due to its high mineral content, yet highly adaptive as it is dynamically remodeled throughout life to meet our daily needs. The process of bone remodeling is primarily carried out by two types of cells, osteoblasts and osteoclasts. Osteoblasts synthesize the protein matrix that mineralizes to become bone; whereas osteoclasts demineralize and resorb bone. The intricate balance between their activities is critical for bone homeostasis, and any disruption of this harmonious relationship can lead to both systemic and localized diseases, such as osteoporosis, osteolytic malignancies, and periodontitis (Zaidi, 2007). Osteoblasts and osteoclasts are tightly regulated by systemic hormones and locally produced cytokines, such as bone morphogenetic proteins (BMPs) (Biver, Hardouin, & Caverzasio, 2013; Giannoudis, Kanakaris, & Einhorn, 2007). BMPs have long established themselves as direct positive regulators of osteoblastic activity; however, their influences on osteoclasts have been controversial. Recent work from the Gopalakrishnan/Mansky lab has provided convincing evidence that BMP signaling directly upregulates osteoclastogenesis induced by RANKL and M-CSF (Broege et al., 2013; Jensen et al., 2010; Sotillo Rodriguez et al., 2009). Upon binding of the cell surface BMP receptors, BMPs exert their regulatory effects through the activation of two distinct intracellular pathways: the canonical pathway involving Smad proteins and the non-canonical pathway involving the MAP kinases (Biver et al., 2013). The goal of this project is to further investigate the specific role of the canonical Smad pathway of BMP signaling in osteoclastogenesis.
University of Minnesota M.S. thesis. June 2014. Major: Dentistry. Advisors: Dr. Kim Mansky and Dr. Brent Larson. 1 computer file (PDF); iv, 36 pages.
Huang, Brandon Pei Han.
Smad 1/5 and Smad 4 expression are necessary for osteoclast differentiation.
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