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Updated: Aug 30 2023

Bone Growth Factors

      • Overview of Growth Factors
      • Factor
      • Source
      • Receptor Class
      • Function
      • TGF-B
      • Platelets, bone ECM, cartilage matrix
      • Seronine threonine sulfate
      • Pleiotropic growth factor stimulates undifferentiated mensenchymal cell proliferation 
      • BMP
      • Osteoprogenitor cells, osteoblasts, bone ECM
      • Seronine threonine sulfate
      • Promotes differentiation of mesenchymal cells into chondrocytes and osteoblasts.
      • Promotes differentiation of osteoprogenitors into osteoblasts, influences skeletal pattern formation.
      • FGF
      • Macrophages, mesenchymal cells, chondrocytes, osteoblasts
      • Tyrosine kinase
      • Mitogenic for mesenchymal cells, chondrocytes, and osteoblasts.
      • IGF
      • Bone matrix, osteoblasts, chondrocytes
      • Tyrosine kinase
      • Promotes proliferation and differentiation of osteoprogenitor cells.
      • PDGF
      • Platelets, osteoblasts
      • Tyrosine kinase
      • Mitogen for mesenchymal cells and osteoblasts; macrophage chemotaxis.
  • Bone Morphogenetic Protein (BMP) & SMADs
    • Overview
      • BMPs belong to the TGF-B superfamily
      • BMP 2,4,6, and 7 all exhibit osteoinductive activity
      • BMP 3 does not exhibit osteoinductive activity
      • Mutations in BMP-4 are associated with Fibrodysplasia ossificans progressiva
    • Mechanism
      • osteoinductive
        • leads to bone formation
        • activates mesenchymal cells to transform into osteoblasts and produce bone
        • has been found to increase chondrogenic phenotype and matrix synthesis in intervertebral discs
    • Signaling Pathways and Cellular Targets
      • BMP targets undifferentiated perivascular mesenchymal cells
      • activates a transmembrane serine/threonine kinase receptor that leads to the activation of intracellular signaling molecules called SMADs
        • SMADS are primary intracellular signaling mediators
        • currently eight known SMADs, and the activation of different SMADs within a cell leads to different cellular responses.
    • Clinical applications
      • FDA-approved uses
        • rhBMP-2
          • single-­level ALIF from L2 to ­S1 levels in degenerative disc disease together with the lumbar tapered fusion device (LT Cage; Medtronic)
          • open tibial shaft fractures stabilized with an IM nail and treated within 14 days of the initial injury
        • rhBMP-7
          • as an alternative to autograft in recalcitrant long bone nonunions where use of autograft is unfeasible and alternative treatments have failed
          • as an alternative to autograft in compromised patients (with osteoporosis, smoking or diabetes) requiring revision posterolateral/intertransverse lumbar fusion for whom autologous bone and bone marrow harvest are not feasible or are not expected to promote fusion
      • contraindications
        • pregnancy
        • allergy to bovine type I collagen or recombinant human rhBMP­-2
        • infection
        • tumor
        • skeletal immaturity
  • Transforming Growth Factor-B (TGF-B)
    • Mechanism
      • secreted in a paracrine fashion
      • both osteoblast and osteoclasts synthesize and respond to TGF-B
      • found in fracture hematomas and believed to regulate cartilage and bone formation in fracture callus
      • stimulates production of Type II collagen and proteoglycans by mesenchymal cells.
      • induces osteoblasts to synthesize collagen
    • Signal Pathway & Cellular Targets
      • signal mechanism involves transmembrane serine/threonine kinase receptors
    • Clinical applications
      • TGF-B is used to coat porous coated implants to promote bone ingrowth
  • Insulin-like Growth Factor 1 (IGF-1)
    • Overview
      • IGF-1, formerly known as somatomedin-C, possibly acts by both paracrine and endocrine hormone pathways
      • most abundant growth factor in bone
    • Mechanism
      • the products of the GH-IGF-1 system induce proliferation without maturation of the growth plate and thus induce linear skeletal growth.
      • the action of the thyroid hormone axis is via an active metabolite that enters target cells and signals a nuclear receptor to stimulate both proliferation and maturation of the growth plate. Increased amounts of the active steroid hormone metabolite promote proliferation and maturation of the growth plate
      • IGF-1 may have a role in enhancing bone formation in defects that heal via intramembranous ossification
    • Signal Pathway & Cellular Targets
      • signal mechanism involves tyrosine kinase receptors
  • Insulin-like Growth Factor 2 (IGF-2)
    • Overview
      • more potent than IGF-1
    • Mechanism
      • stimulates type I collagen production
      • stimulates cartilage matrix synthesis
      • stimulates cellular proliferation
      • stimulates bone formation
    • Signal Pathway & Cellular Targets
      • signal mechanism involves tyrosine kinase receptors
  • Fibroblast Growth Factor (FGF)
    • Overview
      • FGF-1 and FGF-2 are most abundant
      • promote growth and differentiation of a variety of cells
        • epithelial cells
        • myocytes
        • osteoblasts
        • chondrocytes
    • Mechanism
      • binds to membrane spanning tyrosine kinase
      • associated with angiogenesis and chondrocyte and osteoblast activation
      • involved in early stages of fracture healing
  • Platelet-derived growth factor (PDGF)
    • Mechanism
      • released from platelets and signals inflammatory cells to migrate to fracture site
      • role in fracture healing and bone repair has not been clearly defined
    • Signal Pathway & Cellular Targets
      • signal mechanism involves tyrosine kinase receptors
  • Peroxisome proliferator-activated receptor gamma (PPAR-gamma or PPARG)
    • Overview
      • key factor demonstrated in adipogenic differentiation of mesenchymal precursor cells in vitro
    • Signal Pathway & Cellular Targets
      • a nuclear binding receptor that binds to DNA and regulates transcription of target genes
    • Clinical and research applications
      • utilized for adipogenic differentiation in vitro
      • agonists are being utilized to attempt treatment of hyperglycemia and hyperlipidemia
      • targeted by thiazolidinediones for treatment of diabetes
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