Osteoblast apoptosis and bone turnover

J. M. Hock, V. Krishnan, J. E. Onyia, Joseph Bidwell, J. Milas, D. Stanislaus, J. M. Hock

Research output: Contribution to journalArticle

165 Citations (Scopus)

Abstract

With the discoveries of different death mechanisms, an emerging definition of apoptosis is the process of cell death associated with caspase activation or caspase-mediated cell death. This definition accepts that caspases represent the final common mechanistic pathway in apoptosis. Apoptosis may be triggered either by activation events that target mitochondria or endoplasmic reticulum or by activation of cell surface "death receptors," for example, those in the tumor necrosis factor (TNF) superfamily. In the postnatal and adult skeleton, apoptosis is integral to physiological bone turnover, repair, and regeneration. The balance of osteoblast proliferation, differentiation, and apoptosis determines the size of the osteoblast population at any given time. Although apoptosis has been recorded in many studies of bone, the selective mechanisms invoked in the different models studied rarely have been identified. This review offers a broad overview of the current general concepts and controversies in apoptosis research and then considers specific examples of osteoblast apoptosis pertinent to skeletal development and to the regulation of bone turnover. In reviewing selected work on interdigital apoptosis in the developing skeleton, we discuss the putative roles of the bone morphogenetic proteins (BMPs), Msx2, RAR-γ, and death inducer obliterator 1 (DIO-1). In reviewing factors regulating apoptosis in the postnatal skeleton, we discuss roles of cytokines, growth factors, members of the TNF pathway, and the extracellular matrix (ECM). Finally, the paradoxical effects of parathyroid hormone (PTH) on osteoblast apoptosis in vivo are considered in the perspective of a recent hypothesis speculating that this may be a key mechanism to explain the anabolic effects of the hormone. An improved understanding of the apoptotic pathways and their functional outcomes in bone turnover and fracture healing may facilitate development of more targeted therapeutics to control bone balance in patients with osteoporosis and other skeletal diseases.

Original languageEnglish (US)
Pages (from-to)975-984
Number of pages10
JournalJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
Volume16
Issue number6
StatePublished - 2001
Externally publishedYes

Fingerprint

Bone Remodeling
Osteoblasts
Apoptosis
Caspases
Skeleton
Cell Death
Tumor Necrosis Factor-alpha
Anabolic Agents
Bone and Bones
Death Domain Receptors
Bone Morphogenetic Proteins
Bone Regeneration
Fracture Healing
Bone Fractures
Cell Surface Receptors
Population Density
Parathyroid Hormone
Endoplasmic Reticulum
Osteoporosis
Extracellular Matrix

Keywords

  • Apoptosis
  • Caspase
  • Osteoblasts

ASJC Scopus subject areas

  • Surgery

Cite this

Hock, J. M., Krishnan, V., Onyia, J. E., Bidwell, J., Milas, J., Stanislaus, D., & Hock, J. M. (2001). Osteoblast apoptosis and bone turnover. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 16(6), 975-984.

Osteoblast apoptosis and bone turnover. / Hock, J. M.; Krishnan, V.; Onyia, J. E.; Bidwell, Joseph; Milas, J.; Stanislaus, D.; Hock, J. M.

In: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, Vol. 16, No. 6, 2001, p. 975-984.

Research output: Contribution to journalArticle

Hock, JM, Krishnan, V, Onyia, JE, Bidwell, J, Milas, J, Stanislaus, D & Hock, JM 2001, 'Osteoblast apoptosis and bone turnover', Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, vol. 16, no. 6, pp. 975-984.
Hock, J. M. ; Krishnan, V. ; Onyia, J. E. ; Bidwell, Joseph ; Milas, J. ; Stanislaus, D. ; Hock, J. M. / Osteoblast apoptosis and bone turnover. In: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2001 ; Vol. 16, No. 6. pp. 975-984.
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