Osteoblasts in bone physiology-mini review

Abstract

Bone structural integrity and shape are maintained by removal of old matrix by osteoclasts and in-situ synthesis of new bone by osteoblasts. These cells comprise the basic multicellular unit (BMU). Bone mass maintenance is determined by the net anabolic activity of the BMU, when the matrix elaboration of the osteoblasts equals or exceeds the bone resorption by the osteoclasts. The normal function of the BMU causes a continuous remodeling process of the bone, with deposition of bony matrix (osteoid) along the vectors of the generated force by gravity and attached muscle activity. The osteoblasts are derived from mesenchymal stem cells (MSCs). Circulating hormones and locally produced cytokines and growth factors modulate the replication and differentiation of osteoclast and osteoblast progenitors. The appropriate number of the osteoblasts in the BMU is determined by the differentiation of the precursor bone-marrow stem cells into mature osteoblasts, their proliferation with subsequent maturation into metabolically active osteocytes, and osteoblast degradation by apoptosis. Thus, the two crucial points to target when planning to control the osteoblast population are the processes of cell proliferation and apoptosis, which are regulated by cellular hedgehog and Wnt pathways that involve humoral and mechanical stimulations. Osteoblasts regulate both bone matrix synthesis and mineralization directly by their own synthetic activities, and bone resorption indirectly by its paracrinic effects on osteoclasts. The overall synthetic and regulatory activities of osteoblasts govern bone tissue integrity and shape.

Keywords: Bone; Wnt; cytokines; hedgehog; mechanotransduction; osteoblast.

Figure 1

Microscopic image of immunohistochemical staining for collagen I (brown color) in cancellous bone sample. Scale bar 200 μm.

Figure 2

Microscopic image of immunohistochemical staining for osteocalcin (brown color) in cancellous bone sample. Scale bar 500 μm.

Figure 3

Microscopic image of normal bone sample (HE staining). Eosinophilic matrix is surrounded by osteoblasts on its edges. Scale bar 200 μm.

Figure 4

Microscopic image of Von Kossa staining (calcium bone nodules stained by 5% silver nitrate) adjacent to cultured human osteoblasts. Scale bar 30 μm.

Figure 5

Interactions between BMU components.

Figure 6

Examples of microscopic images of cells stained by JC-1. A: Control cultured osteoblasts. B: Cultured osteoblasts treated by pro-apoptotic agent (FGIN-1-27). Greater red color staining is apparent in cells treated by pro-apoptotic agent (B) in comparison to untreated osteoblasts (A), indicating a decrease in the mitochondrial membrane potential. Confocal microscopy. Scale bar 30 μm.

Figure 7

Microscopic imaging (confocal microscopy) of human osteoblasts stained by Mito Tracker Green stain, which is specific to mitochondria. The high content of mitochondria in human osteoblasts is evident. Scale bar 10 μm.