JBJS | The Role of Activating Transcription Factor-2 in Skeletal Growth Control

The Journal of Bone & Joint Surgery, Volume 85, Issue suppl 2

Scientific Article | April 01, 2003

The Role of Activating Transcription Factor-2 in Skeletal Growth Control

Phyllis Luvalle, PhD; Qin Ma, DDS, PhD; Frank Beier, PhD

The Journal of Bone & Joint Surgery. 2003; 85:133-136

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The growth plate is a dynamic area of cells that directs longitudinal bone growth and endochondral ossification by virtue of the progression of chondrocytes through the proliferation, maturation, and hypertrophic stages of cell differentiation. The initiation of growth-plate chondrocyte proliferation is stimulated by growth-hormone-induced IGF-1 ¹ , followed by rapid clonal proliferation in response to a variety of growth factors. The chondrocytes exit the cell cycle after multiple cycles of proliferation to form a maturation, or prehypertrophic, zone. Here, chondrocytes sustain substantial increases in cell volume and, coincident with type-X collagen expression, mature to become hypertrophic chondrocytes. Mineralization of the cartilage matrix as well as vascular invasion, which introduces marrow and osteoblast precursors, occurs within the lowermost hypertrophic zone. Osteoblasts secrete bone matrix as well as proteases that break down the cartilage matrix. The hypertrophic chondrocytes undergo apoptosis, leaving behind osseous trabeculae that contribute to the microenvironment of the marrow. Both proliferation and hypertrophy are necessary for longitudinal bone growth ² . Proliferation initiates longitudinal growth and provides sufficient cells to undergo hypertrophy, while the large increase in cell diameter resulting from maturation and hypertrophy contributes substantially to bone length. Activating transcription factor-2 (ATF-2) is expressed only in the resting and proliferative zones of endochondral growth plates ³ . Many studies, including our own, have suggested that ATF-2 has multiple roles in the control of skeletal growth ^3-5 by virtue of its ability to control the expression of a variety of genes that promote or inhibit chondrocyte proliferation and growth-plate progression.

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Topics

cell cycle ; chondrocytes ; cyclin a ; cyclin d1 ; dna ; epiphysial cartilage ; retinoblastoma protein ; house mice ; lab mice ; transcription factor

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These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.

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