Upregulation of basal TGFβ₁ levels by EMF coincident with chondrogenesis – implications for skeletal repair and tissue engineering

Abstract

Members of the TGFP/BMP gene family regulate cartilage and bone development. These genes are re-expressed in bone repair and are thought to mediate chondro-and osteoprogenitor cell differentiation. These observations have led to a therapeutic strategy of introducing these growth factors into experimental cartilage and bone defects. Therapeutic efficacy, however, has been limited by diffusion or inactivation of these growth factors from the desired site and by the inability to deliver sustained concentrations of growth factors. This study demonstrates an increase in basal TGFP mRNA and protein levels in association with chondrogenic differentiation in endochondral ossification. mRNA is increased by 158%; protein by 23%, and cells immunopositive for TGFP by 343% at maximal TGFP expression. Importantly, the pattern of TGFP expression is preserved throughout the developmental sequence. Our data suggest that the exposure to a specific electromagnetic field (EMF) enhances, but does not disorganize, chondrogenesis and endochondral calcification as well as the normal physiologic expression of TGFP. The ability to increase TGFP at a moderately low dose for sustained periods of time without disorganizing its physiology suggests the ability to establish temporal concentration gradients of growth factors for the purpose of stimulating skeletal repair.

Treatment of osteochondral defects of the talus

“…47 In vitro and in vivo studies showed that PEMF stimulation leads to an increase of transforming growth factor b, thereby improving bone development, reducing cartilage damage and increasing chondrocyte proliferation. 6,47,83,98 Clinical studies showed promising results for fracture nonunion and for recovery after arthroscopic treatment of focal cartilage knee lesions. 161,462 Therefore, PEMF stimulation may be effective for talar OCDs after arthroscopic treatment by producing effects that suppress inflammation, promote tissue healing, and relieve pain.…”

“…436 In vitro and in vivo studies have shown that PEMFs act as adenosine A2a agonists, leading to an increase of transforming growth factor b-1, thereby improving bone development, reducing cartilage damage and increasing chondrocyte proliferation. 6 Clinically, its favorable eff ects are less obvious. PEMF as a solitary treatment for osteoarthritis of the knee has been repeatedly investigated, with confl icting results.…”

Electrical stimulation therapies for spinal fusions: current concepts

“…Most investigations on the mechanism of action of IC technology have been performed with the PEMF signal which is FDA approved for fracture healing but not spinal fusion [1,4,8,11,29,43,44,51,64]. There is only one study using the PEMF signal that is clinically approved for spinal fusions [61] and a few studies with CMF [11,20,21,58].…”

Pulsed electromagnetic field therapy results in healing of full thickness articular cartilage defect

“…These in vitro studies have shown that chondrocyte proliferation and matrix synthesis are significantly enhanced by PEMF stimulation [8,9]. In vivo, it up-regulates the gene expression of growth factor TGF-β and prevents the catabolic effects of inflammatory cytokines [1,2,9].…”

“…This treatment has well documented physiological effects on cells and tissues such as the upregulation of gene expression of members of the TGF-β (transforming growth factor) super family [1,2]. It also enhances chondrogenic proliferation, differentiation and synthesis of cartilage extracellular matrix proteins [8,9].…”