Treatment of cartilage–hair hypoplasia with recombinant human growth hormone

Abstract

Cartilage-hair hypoplasia (CHH) is an autosomal recessive disorder characterized by short stature, hypoplastic hair and humoral immunity disorders. It is a mutation in the RMRP gene, located on chromosome 9p13.3, that leads to CHH. There is no special treatment for short stature in CHH. The efficacy and safety of recombinant human growth hormone (rhGH) therapy in CHH is still under discussion. The present study describes the case of a girl with CHH who was treated with rhGH. The rhGH treatment had a significant effect on the height gain: the height SD score was changed from -4. to -2.98 after 4 years 7 months of treatment. rhGH therapy should be considered as a treatment modality for CHH, and insulin-like growth factor (IGF)-1 and IGF-binding protein 3 concentrations should be closely monitored, particularly because of the increased cancer risk that is a characteristic feature of CHH.

Small nucleolar RNAs in chondorgenic differentiation and osteoarthritis

“…The involvement of the RMRP lncRNA in the pathophysiology of CHH has previously been identified 17 we examined the expression of viperin, determined its role in chondrocyte protein secretion, and investigated its crosstalk with the TGF-β/SMAD2/3 signaling pathway in chondrogenic differentiation. We discovered that viperin is expressed in differentiating chondrocytic cells, regulates their protein secretion and impacts the outcome of the chondrogenic differentiation program through influencing TGF-β/SMAD2/3 activity via CXCL10.…”

“…Transcription factors Runx2 and Mef2c drive the expression of type X collagen (Col10a1) 15,16 during the hypertrophic phase of chondrogenic differentiation. Together with alkaline phosphatase (Alpl) 17 , these proteins are major markers for the hypertrophic phase of chondrogenic differentiation.…”

“…CHH is caused by mutations in RMRP RNA 14,17 , but it is unknown whether these mutations influence chondrogenic differentiation in CHH patients. To test whether the chondrogenic capacity of CHH cells is impaired, we employed a trans-differentiation protocol that drives dermal fibroblasts towards a chondrocyte-like phenotype 34 Figure 8E).…”

“…ATDC5 cells 17 (RIKEN BRC, Japan) were cultured in a humidified atmosphere at 37 o C, 5% CO2 in proliferation medium (DMEM/F12 (Invitrogen, Carlsbad, CA, USA), 5% FCS (Sigma-Aldrich, St. Louis, MO, USA) and 1% antibiotic/antimycotic (Invitrogen). Cells were plated at 6,400 cells/cm 2 .…”

“…RNase P is critically involved in maturation of tRNAs by cleaving the 5' leader of pre-tRNA and is involved in RNA polymerase I and III transcriptional activity 11-13 . Mutations in the RMRP gene are the cause of a severe form of dwarfism known as the cartilage-hair hypoplasia 14 (CHH: OMIM #250250) -anauxetic dysplasia 15 (AAD: OMIM #607095) spectrum of disorders 16 . CHH is also termed metaphyseal chondrodysplasia, McKusick-type 17 . To date, more than hundred individual CHH-pathogenic mutations have been identified in the RMRP gene 14 .…”