Role of transforming growth factor-beta in bone remodeling

L. F. Bonewald, G. R. Mundy

Research output: Contribution to journalReview articlepeer-review

354 Scopus citations


Transforming growth factor-beta (TGF-β) plays a critical role in bone remodeling. TGF-β stimulates matrix protein synthesis, has dramatic effects on the bone cells responsible for bone formation and resorption, and is abundant in bone and bone-conditioned media. Multiple sources of TGF-β have been described. It was initially purified from platelets. Two distinct forms of TGF-β have been purified from bone. The second form, TGF-βII, was initially purified from bone but was then identified in platelets and also as the major TGF-β in the monkey kidney BSC-1 cell line. The two bone-derived factors were called cartilage-inducing Factor A (CIF-A) and cartilage-inducing Factor B (CIF-B), based on their capacity to induce the formation of extracellular matrix proteins, which are characteristic of cartilage. CIF-A is identical to the TGF-β purified from platelets, which is called TGF-βI. CIF-B is the same as TGF-βII, which was sequenced soon after CIF-B was discovered and characterized. There is 70% sequence homology between the two forms. The largest source of TGF-β in the body is present in bone (200 μg/kg tissue), although the most concentrated source is in platelets. TGF-β has multiple effects on bone cells depending on their phenotype and/or stage of differentiation. Osteoblasts, the cells responsible for formation of new bone and perhaps cellular control of bone remodeling, are directly affected by TGF-β, which can induce differentiation or proliferation, depending on the osteoblastic cell type examined. TGF-β inhibits the formation of osteoclast precursors and bone resorption and, in greater concentrations, has inhibitory effects on isolated osteoclasts, the cells responsible for bone resorption. TGF-β may act as a bone-coupling factor linking bone resorption to bone formation.

Original languageEnglish (US)
Pages (from-to)261-276
Number of pages16
JournalClinical Orthopaedics and Related Research
StatePublished - 1990

ASJC Scopus subject areas

  • Surgery
  • Orthopedics and Sports Medicine


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