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Growth and Cartilage Biology


The skeleton provides support and protection to soft tissues and internal organs. It is crucial to our ability to move and it is also the body’s mineral storage and host for hematopoesis. Skeletal diseases comprise a varied group of disorders that affects the formation, growth, mineralization, and/or remodeling of the skeleton. In our research, we explore the cellular and molecular mechanisms of growth and skeletal disorders, and this knowledge is then applied to improve diagnosis and medical treatments of skeletal disorders as there for most of these diseases, are no or only imperfect treatments available.

Longitudinal bone growth occurs at the growth plate by a process called endochondral ossification in which cartilage is first formed and then remodeled into bone tissue.  The growth plate is a layer of cartilage found near the ends of long bones, between the epiphysis and the metaphysis. The growth plate consists of three histologically and functionally discrete layers: 1) the resting zone. We previously demonstrated that the resting zone contains stem-like cells (unipotent stem cells, equivalent to stem cells in the skin and the intestines) which renew the pool of proliferative cells, 2) the proliferative zone, where chondrocytes actively proliferate and line up in columns, thereby directing growth primarily in one dimension, and 3) the hypertrophic zone, where the terminally differentiated chondrocytes calcify their matrix and attracts the invading bone and endothelial cells, a crucial step in endochondral bone formation.


Our research in translational growth and skeletal disorders combine unique and well-characterized patient cohorts, advanced genetic and bioinformatic methods with genetic targeting in mice, cellular model systems and molecular biology methods. This research investigates the underlying molecular causes responsible for childhood growth and skeletal disorders. Ultimately, based on our data, we select specific genes or molecular mechanism that could be suitable targets for novel treatment strategies that will be tested in animals.

This research has immediate benefit for the patients suffering from genetic growth disorders as it will identify the underlying genetic diagnosis, thus enabling more accurate information about the cause, mode of inheritance, and prospects of improving their medical care. Understanding skeletal development, physiology, and pathology would offer novel treatment strategies for growth and skeletal diseases. It is highly important for several other large patient groups including children with inflammatory diseases and children treated for cancer who often develop growth problems.

Selected publications

Zhang Y, Zhao S, Hallgrimsdottir S, Zuo Y, Li X, Liu S, Lindelöf H, Wang S, Hammarsjö A, Batkovskyte D, Ye Y, Wang L, Yan Z, Lin J, Yu C, Chen z, Niu Y, Wang H, Zhao Z, Liu P, Qiu G, Posey JE, Wu Z, Lupski JR, Micule I, Anderlid BM, Voss U, Sulander D, Kuchinskaya E, Nilsson O, Zhang TJ, Grigelioniene G, Wu N. Expanding the mutation and phenotype spectrum of MYH3-related skeletal disorders. NPJ Genom Med. 2022 Feb 15;7(1):11.


Lennartson O, Lodefalk M, Wethje H, Stattin EL, Sävendahl L, Nilsson O. Bilateral epiphysiodesis due to extreme tall stature in a girl with a de novo DNMT3A variant associated with Tatton-Brown-Rahman syndrome. Front Endocrinol (Lausanne). 2021 Oct 13;12:752756.


Dou Z, Muder D, Baroncelli M, Bendre A, Gkourogianni A, Ottosson L, Vedung T, Nilsson O. Rat perichondrium transplanted to articular cartilage defects forms articular-like, hyaline cartilage. Bone. 2021 Jun 8;151:116035. doi: 10.1016/j.bone.2021.116035.


Dou Z, Chau M, Muder D, Vedung T, Nilsson O. Optimized protocols for in situ hybridization, immunohistochemistry, and immunofluorescence on skeletal tissue. Acta Histochem 2021 Jun 30;123(5):151747.


Gkourogianni A, Andrade AC, Segerlund E, Werner-Sperker A, Jonsson BA, Horemuzova E, Dahlgren J, Burstedt M, Nilsson O. Pre and postnatal growth failure with microcephaly due to two novel heterozygous IGF1R mutations and response to growth hormone treatment. Acta Paediatr. 2020 Oct;109(10):2067-2074.


Nilsson O. Aggrecanopathies highlight the need for genetic evaluation of selected ISS children: Commentary on “High frequency of pathogenic ACAN variants including an intragenic deletion in selected individuals with short stature.” Invited commentary. Eur J Endocrinol. 2020Aug;183(2):C9-C10.


Imel EA, Glorieux FH, Whyte MP, Munns CF, Ward L, Nilsson O, Simmons JH, Padidela R, Namba N, Cheong HI, Pitukcheewanont P, Sochett E, Högler W, Muroya K, Tanaka H, Gottesman GS, Biggin A, Perwad F, Mao M, Chen CY, Skrinar A, San Martin J, Portale AA. Burosumab vs. continuation of conventional therapy in children with X-linked hypo-phosphatemia: a randomised, active-controlled, open-label, phase 3 trial. Lancet. 2019 Jun 15;393(10189):2416-2427.


Jee YH, Baron J, Nilsson O. New developments in the genetic diagnosis of short stature. Curr Opin Pediatr. 2018 Aug;30(4):541-547.


Lui JC, Barnes KM, Dong L, Yue S, Graber E, Rapaport R, Dauber A, Nilsson O, Baron J. Ezh2 mutations found in the Weaver overgrowth syndrome cause a partial loss of H3K27 histone methyltransferase activity. J Clin Endocrinol Metab. 2018 Apr 1;103(4):1470-1478. 


Gkourogiannin A, Andrew M, Tyzinski L, Crocker M, Douglas J, Dunbar N, Fairchild J, Funari MF, Heath KE, Jorge AA, Kurtzman T, LaFranchi S, Lalani S, Lebl J, Lin Y, Los E, Newbern D, Nowak C, Olson M, Popovic J, Průhová Š, Elblova L, Quintos JB, Segerlund E, Sentchordi L, Shinawi M, Stattin EL, Swartz J, Ariadna GA, Sinhué DC, Hosono H, Sanchez-Lara PA, Hwa V, #, Dauber A#. Clinical characterization of patients with autosomal dominant short stature due to aggrecan mutations. #Contributed equally. J Clin Endocrinol Metab. 2017 Feb 1;102(2):460-469. 


Lui JC, Garrison P, Nguyen Q, Ad M, Keembiyehetty C, Chen W, Jee YH, Landman E, Nilsson O, Barnes KM, Baron J. Histone methyltransferases EZH1 and 2 promote skeletal growth by repressing inhibitors of chondrocyte proliferation and hypertrophy. Nature Commun. 2016 Nov 29;7:13685.


Baron J, Sävendahl L, De Luca F, Dauber A, Phillip M, Wit JM, Nilsson O. Short and tall stature: a new paradigm emerges. Nat Rev Endocrinol. 2015 Dec;11(12):735-46.


Nilsson O, Guo M, Dunbar N, Popovic J,  Flynn D,  Jacobsen C, Lui JC, Hirschhorn JN, Baron J,  Dauber A. Short stature, accelerated bone maturation, and early growth cessation due to heterozygous aggrecan mutations. J Clin Endocrinol Metab. 2014 Aug;99(8):E1510-8.


Lui JC, Nilsson O, Chan Y, Palmer CD, Andrade AC, Hirschhorn JN, Baron J. Synthesizing genome-wide association studies and expression microarray reveals novel genes that act in the human growth plate to modulate height.  Hum Mol Genet 2012 Dec 1;21(23):5193-5201.


Julian C. K. Lui, Anenisia C. Andrade, Anita Hegde, WeiPing Chen, Jeffrey Baron, Ola Nilsson. Spatial and Temporal Regulation of Gene Expression in the Mammalian Growth Plate. Bone. 2010 May;46(5):1380-90.

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