Figure 10.

Old versus new views regarding cells responsible for bone mineralization and the onset of rickets. (a). The prevailing theory in bone biology is that new bone is formed by osteoblasts (Obs) from the bone surface. (b). The new model (that Ocys form mineralized bone) includes the following four key components. i). Nascent Ocys (dark grey) produce collagen matrixes and small amounts of mineral (Ca-Pi) surrounding the “wire-mesh” built by Ocys-dendrites. ii). Working together, the well-formed Ocys (light grey) and the mature Ocys (white) deposit Ca-Pi in the bone matrices, “pump” Ca-Pi to the bone surfaces(two green lines with numerous “thorns” indicating the mineral that originated from the inner Ocys), and fill in the early formed Ocy space(blue). This space is greatly depleted during the long, slow bone maturation process; iii). Ocys directly take Ca, Pi, and nutrients from the blood vessels; iv). DMP1 and Phex are the key molecules controlling the differentiation of Obs to Ocys and the subsequent Ocy maturation; v) The matured Ocys produce SOST (sclerostin, a potent inhibitor of Wnt-β-catenin) to maintain Wnt signaling at a low level. (c). In the Dmp1-null (KO) or Phex mutation (Hyp) mice, the immature bone cells release large amounts of β-catenin (β-Cat), which accelerates cell proliferation but inhibits cell differentiation. As a result, the defective bone cells that are arrested either at the late Ob stage (although preserving high Ob activity; blue cells) or at the immature Ocy stage (grey cells) fail to “pump” enough Ca-Pi to the surrounding bone matrices and bone surfaces (red, osteoid; green, mineralized matrices), leading to osteomalacia. (d). The real 3d view of healthy OCYs (left) versus Ob-like cells in rickets bone (right) by use of a newly established VolumeScope technique.