title: Genetically engineered flavonol enriched tomato fruit modulates chondrogenesis to increase bone length in growing animals.
abstract: Externally visible body and longitudinal bone growth is a result of proliferation of chondrocytes. In growth disorder, there is delay in the age associated increase in height. The present study evaluates the effect of extract from transgenic tomato fruit expressing AtMYB12 transcription factor on bone health including longitudinal growth. Constitutive expression of AtMYB12 in tomato led to a significantly enhanced biosynthesis of flavonoids in general and the flavonol biosynthesis in particular. Pre-pubertal ovary intact BALB/c mice received daily oral administration of vehicle and ethanolic extract of wild type (WT-TOM) and transgenic AtMYB12-tomato (MYB12-TOM) fruits for six weeks. Animal fed with MYB12-TOM showed no inflammation in hepatic tissues and normal sinusoidal Kupffer cell morphology. MYB12-TOM extract significantly increased tibial and femoral growth and subsequently improved the bone length as compared to vehicle and WT-TOM. Histomorphometry exhibited significantly wider distal femoral and proximal tibial growth plate, increased number and size of hypertrophic chondrocytes in MYB12-TOM which corroborated with micro-CT and expression of BMP-2 and COL-10, marker genes for hypertrophic cells. We conclude that metabolic reprogramming of tomato by AtMYB12 has the potential to improve longitudinal bone growth thus helping in achievement of greater peak bone mass during adolescence.
authors.affiliation: CSIR-Central Drug Research Institute (CSIR-CDRI), Endocrinology Division, Jankipuram Extension, Sitapur Road, Lucknow-226031, INDIA.
authors.forename: Dharmendra
authors.initials: D
authors.lastname: Choudhary
authors.affiliation: CSIR-National Botanical Research Institute (CSIR-NBRI), Rana Pratap Marg, Lucknow-226 001, INDIA.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Pandey
authors.affiliation: CSIR-Central Drug Research Institute (CSIR-CDRI), Endocrinology Division, Jankipuram Extension, Sitapur Road, Lucknow-226031, INDIA.
authors.forename: Sulekha
authors.initials: S
authors.lastname: Adhikary
authors.affiliation: CSIR-Central Drug Research Institute (CSIR-CDRI), Endocrinology Division, Jankipuram Extension, Sitapur Road, Lucknow-226031, INDIA.
authors.forename: Naseer
authors.initials: N
authors.lastname: Ahmad
authors.affiliation: CSIR-National Botanical Research Institute (CSIR-NBRI), Rana Pratap Marg, Lucknow-226 001, INDIA.
authors.forename: Chitra
authors.initials: C
authors.lastname: Bhatia
authors.affiliation: CSIR-National Botanical Research Institute (CSIR-NBRI), Rana Pratap Marg, Lucknow-226 001, INDIA.
authors.forename: Sweta
authors.initials: S
authors.lastname: Bhambhani
authors.affiliation: CSIR-National Botanical Research Institute (CSIR-NBRI), Rana Pratap Marg, Lucknow-226 001, INDIA.
authors.forename: Prabodh Kumar
authors.initials: PK
authors.lastname: Trivedi
authors.affiliation: CSIR-Central Drug Research Institute (CSIR-CDRI), Endocrinology Division, Jankipuram Extension, Sitapur Road, Lucknow-226031, INDIA.
authors.forename: Ritu
authors.initials: R
authors.lastname: Trivedi
mesh_terms: D000818:Animals; D029681:Arabidopsis Proteins; D020219:Chondrogenesis / Q000187:drug effects*; D005260:Female; D044948:Flavonols / Q000096:biosynthesis / Q000494:pharmacology*; D005638:Fruit / Q000737:chemistry; D018551:Solanum lycopersicum / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D030821:Plants, Genetically Modified / Q000737:chemistry / Q000378:metabolism; D014157:Transcription Factors
chemical_list: D029681:Arabidopsis Proteins; D044948:Flavonols; C504539:MYB12 protein, Arabidopsis; D014157:Transcription Factors