Osteoclast formation and function and its role in skeletal bone disease

Monique Bethel, Angela Bruzzaniti, Melissa A. Kacena

Research output: Chapter in Book/Report/Conference proceedingChapter


Osteoclasts are highly specialized cells, derived from the hematopoietic lineage, that resorb mineralized bone matrix. Osteoclast precursors can be recruited to the bone remodeling sites by specific cytokines in the microcellular environment, including some secreted by osteoblasts, fibroblasts, and osteocytes. Once the mononuclear osteoclast precursors converge on the bone surface, they fuse into large, multinucleated cells, a process that results in a highly efficient bone-resorbing cell. Cytoskeletal rearrangement then occurs, polarizing the cell such that the area of the cell directly in contact with the bone surface forms a sealing zone surrounding the ruffled border membrane which provides a large surface area for resorption. In the normal physiologic state, bone resorption and formation are tightly linked. However, several diseases have been identified where dysregulated bone resorption leads to bone of abnormal quality. Overly active osteoclasts have been implicated in the bone loss that occurs in a diverse set of diseases including osteoporosis, cancer, and inflammatory arthritis. Conversely, in osteopetrosis, underactive osteoclasts can lead to abnormally dense bone. In either situation, high or low bone mass, the poor bone quality leads to increased risk of fracture. Here we will review the current knowledge of the cellular events that recruit osteoclasts to sites of bone remodeling, initiate differentiation and fusion, and induce the cytoskeletal rearrangements that prepare the cell for bone resorption. Furthermore, we will examine how disruptions in any one or several of these processes create abnormalities in osteoclast morphology and function and contribute to skeletal disease in humans.

Original languageEnglish (US)
Title of host publicationOsteoclasts
Subtitle of host publicationMorphology, Functions and Clinical Implications
PublisherNova Science Publishers, Inc.
Number of pages22
ISBN (Print)9781620813065
StatePublished - Sep 2012
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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