BMP‐6 and BMPR‐1a are up‐regulated in the growth plate of the fractured tibia

Abstract

Bone overgrowth is a known phenomenon occurring after fracture of growing long bones with possible long-term physical consequences for affected children. Here, the physeal expression of bone morphogenetic proteins (BMPs) was investigated in a fractureanimal model to test the hypothesis that a diaphyseal fracture stimulates the physeal expression of these known key regulators of bone formation, thus stimulating bone overgrowth. Sprague-Dawley rats (male, 4 weeks old), were subjected to a unilateral mid-diaphyseal tibial fracture. Kinetic expression of physeal BMP-2, -4, -6, -7, and BMP receptor-1a (BMPR-1a) was analyzed in a monthly period by quantitative real time-polymerase chain reaction and immunohistochemistry. On Days 1, 3, 10, and 14 post-fracture, no changes in physeal BMPs gene-expression were detected. Twenty-nine days post-fracture, when the fracture was consolidated, physeal expression of BMP-6 and BMPR-1a was significantly upregulated in the growth plate of the fractured and contra-lateral intact bone compared to control (p < 0.005). This study demonstrates a late role of BMP-6 and BMPR-1a in fracture-induced physeal growth alterations and furthermore, may have discovered the existence of a regulatory ''cross-talk'' mechanism between the lower limbs whose function could be to limit leg-length-discrepancies following the breakage of growing bones. ß

TGF‐β activity in acid bone lysate adsorbs to titanium surface

“…The results of the current study showed that TGF‐β activity of acid‐bone lysates adsorbs to titanium implant surfaces. This TGF‐β activity was determined by a bioassay showing the expression of the respective target genes, including IL11 and NOX4, but also BMP2 and BMP6, both being growth factors relevant for bone regeneration and MMP10, MMP13, and PAI‐1, together regulating the remodeling of extracellular matrix . Also, CTGF being among the target genes, is critically involved in wound healing and in fibrotic pathologies .…”

RECENT RESEARCH ON THE GROWTH PLATE: Mechanisms for growth plate injury repair and potential cell-based therapies for regeneration

“…These effects were found regardless whether the growth plate was injured or not. For example, Fischerauer et al (2013) found that following a tibial fracture, there were up-regulated levels of BMP6 and BMP receptor BMPR1A at the growth plate of the fractured or the contralateral intact bones on day 29 (when fractured bone was consolidated), suggesting possibly a late role of BMP6 and BMPR1A in bone fracture-induced growth plate alterations and the potential existence of a regulatory 'cross-talk' mechanism between the different regions of the lower limbs after bone fractures (Fischerauer et al 2013). A recent study by Macsai et al (2011) evaluated injured growth plate of rats by micro-CT (Macsai et al 2011) and found the presence of small bony 'tethers' at the uninjured adjacent growth plate on day 60 post-injury.…”

Impairment of maturation of BMP-6 (35kDa) correlates with delayed fracture healing in experimental diabetes

“…chondrogenesis and early osteogenesis. Moreover, the early up-regulation of the BMP-6 (35kDa) may be derived by the post-translational mechanism, because neither difference in the transcription copies of the mRNA coding BMP-6 nor the BMP-6 proteins with higher molecular weights than 35kDa was detected in previous studies [18,24,25].…”

“…Although the potential participation of BMP-6 in bone formation was indicated in previous researches [18,[24][25][26], the role of the compound in diabetes related impairment of fracture healing has not been elucidated. The novel finding of this study indicates a particular member of the BMP-6 family, with a molecular weight of 35 kDa, may play an important role in fracture healing.…”