Figure 1.

Current understanding of osteogenesis and bone remodeling. (A) Flat bones are formed through intramembranous ossification, cells are originated from the cranial neural crest (CNC). Limb bones are formed through endochondral ossification (details shown in (C)), cells are originated from the mesoderm-derived limb bud (LB) mesenchyme. (B) Two major routes for osteoblast differentiation. Mesoderm cells give rise to mesenchymal osteochondroprogenitors (OCPs) which can diverge into chondrocytic and osteoblastic lineages. Chondrocytes undergo hypertrophy and a portion of them differentiate into osteoblasts at the chondro-osseous junction. Neural crest-derived mesenchymal progenitors can differentiate directly to osteoblasts during intramembraneous ossification. (C) Endochondral ossification is a process of converting cartilage to bone and is essential for bone elongation. Cartilage anlagen of a future bone forming in the limb bud during embryogenesis. Chondrocyte hypertrophy (HC) initiates in the center of the anlagen where blood vessels (BVs) invade, bringing in osteoprogenitors and bone marrow cells. The primary spongiosa (PS) separates the cartilage into proximal and distal growth plates (GPs). From childhood to adolescence, there is an active proliferation of chondrocytes prior to hypertrophy, and the mineralizing cartilage is replaced by bone at the chondro-osseous junction (COJ). Thickening of cortical bone continues from birth to puberty when the GPs become inactive. (D) Bone remodeling maintains the integrity and homeostasis of bone in adulthood. Osteoclasts are bone resorptive cells originated from hematopoietic stem cells (HSCs). They remove microfractured segments of bone and mobilize osteoblasts to form new bone. Osteomorphs are a novel cell type generated through fission of osteoclasts. Subsequent fusion of osteomorphs can reform active osteoclasts. Multiple sources of skeletal stem cells (SSCs) and OCPs have been identified as the source of osteoblasts for bone formation. Some of the mature osteoblasts are embedded into the osteoid and further differentiate into osteocytes which have a critical role in bone remodeling coordination.