Charlene J Williams1. 1. Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, New Jersey, USA.
Abstract
PURPOSE OF REVIEW: ANKH is the human homolog of a gene whose dysfunction in a mutant mouse strain results in progressive ankylosis of the spine as well as soft tissue mineralization. ANKH mutations have been reported in inherited human disorders such as familial calcium pyrophosphate deposition disease (CPPD) and cranial metaphyseal dysplasia; however, research into the function of the ANKH protein has been more challenging. Progress has recently been made to understand the role of ANKH in the regulation of physiological and pathological mineralization. RECENT FINDINGS: ANKH expression is regulated by intracellular levels of oxygen, phosphate and calcium as well as by the growth factor TGF-β. In addition, ANKH expression affects chondrogenesis, osteoblastogenesis and osteoclastogenesis. ANKH appears to interact with several cellular proteins, including the phosphate transporter PiT-1, and with proteins involved in NF-kappa β signaling, suggesting that ANKH may play an important non-PPi transporter role. ANKH has also been shown to regulate ATP efflux from chondrocytes. SUMMARY: ANKH expression, as well as its potential non-PPi transporter functions, plays a variety of roles in the regulation of cellular events that surround differentiation and mineralization in bone and cartilage. Additional studies are warranted to further elucidate the contributions of ANKH to human health and disease, and to determine if ANKH deserves targeting for the treatment of diseases such as CPPD.
PURPOSE OF REVIEW: ANKH is the human homolog of a gene whose dysfunction in a mutant mouse strain results in progressive ankylosis of the spine as well as soft tissue mineralization. ANKH mutations have been reported in inherited human disorders such as familial calcium pyrophosphate deposition disease (CPPD) and cranial metaphyseal dysplasia; however, research into the function of the ANKH protein has been more challenging. Progress has recently been made to understand the role of ANKH in the regulation of physiological and pathological mineralization. RECENT FINDINGS:ANKH expression is regulated by intracellular levels of oxygen, phosphate and calcium as well as by the growth factor TGF-β. In addition, ANKH expression affects chondrogenesis, osteoblastogenesis and osteoclastogenesis. ANKH appears to interact with several cellular proteins, including the phosphate transporter PiT-1, and with proteins involved in NF-kappa β signaling, suggesting that ANKH may play an important non-PPi transporter role. ANKH has also been shown to regulate ATP efflux from chondrocytes. SUMMARY:ANKH expression, as well as its potential non-PPi transporter functions, plays a variety of roles in the regulation of cellular events that surround differentiation and mineralization in bone and cartilage. Additional studies are warranted to further elucidate the contributions of ANKH to human health and disease, and to determine if ANKH deserves targeting for the treatment of diseases such as CPPD.
Authors: Cornelia D Cudrici; Kam A Newman; Elisa A Ferrante; Rebecca Huffstutler; Katherine Carney; Blas Betancourt; Markku Miettinen; Richard Siegel; James D Katz; Leon J Nesti; Cynthia St Hilaire; Deepak Lakshmipathy; Han Wen; Mohammad H Bagheri; Manfred Boehm; Alessandra Brofferio Journal: Rheumatology (Oxford) Date: 2021-12-24 Impact factor: 7.580
Authors: Clara Sanjurjo-Rodriguez; Thomas G Baboolal; Agata N Burska; Frederique Ponchel; Jehan J El-Jawhari; Hemant Pandit; Dennis McGonagle; Elena Jones Journal: Sci Rep Date: 2019-06-27 Impact factor: 4.379