J Ayub Med Coll Abbottabad 2017 Apr-Jun;29(2):350-352

Department of Paediatrics and Neonatology, Ayub Medical College Abbottabad, Pakistan.

Two main forms of osteopetrosis are recognized, a severe autosomal recessive form (MIM 259700) with an incidence of approximately 1 in 250,000 births and a mild autosomal dominant form (MIM166600) with an incidence of 1 in 20,000 births. Intrinsic disturbances of osteoclastic function due to mutations in genes encoding osteoclast-specific subunits of the vacuolar proton pump (TCIRG1, CLCN7) are found in most patients with recessive form. Mutations of CLCN7 are observed in dominant form of osteopetrosis . Read More

J Clin Endocrinol Metab 2017 Jun 26. Epub 2017 Jun 26.

Departments of Medicine (CW) and Pediatrics (LEP), Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.

Background: Osteopetrosis encompasses a group of rare metabolic bone diseases characterized by impaired osteoclast activity or development, resulting in high bone mineral density. Existing guidelines focus on treatment of the severe infantile forms with hematopoietic cell transplantation (HCT), but do not address the management of patients with less severe forms for whom HCT is not the standard of care. Therefore, our objective was to develop expert consensus guidelines that would address the management of these patients. Read More

Eur J Hum Genet 2017 Jun 14. Epub 2017 Jun 14.

Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital Duesseldorf, Heinrich Heine University, Düsseldorf, Germany.

Coexistence of different hereditary diseases is a known phenomenon in populations with a high consanguinity rate. The resulting clinical phenotypes are extremely challenging for physicians involved in the care of these patients. Here we describe a 6-year-old boy with co-occurrence of a homozygous splice defect in OSTM1, causing infantile malignant osteopetrosis, and a loss-of-function variant in MANEAL, which has not been associated with human disease so far. Read More

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2017 Jun;34(3):377-381

Department of Hematology, Anhui Provincial Children's Hospital, Hefei, Anhui 230001, China.

Objective: To detect potential mutation of the TCIRG1 gene in a boy with infantile malignant osteopetrosis.

Methods: Target sequence capture and next-generation sequencing were applied for the proband and his parents to identify the causative mutation, and Sanger sequencing was used to verify the suspected mutation.

Results: The proband manifested at 4 months of age with symptoms including anemia, thrombocytopenia, hepatosplenomegaly, and cephalus quadratus. Read More

Strategies Trauma Limb Reconstr 2017 Jun 7. Epub 2017 Jun 7.

Russian Ilizarov Scientific Center for Restorative Traumatology and Orthopaedics, 6, M.Ulyanova Street, Kurgan, Russian Federation, 640014.

Autosomal dominant osteopetrosis (Albers-Schönberg disease) classically displays the radiographic signs of osteosclerosis. The main ADO complications involve the skeleton: low-impact bone fractures, scoliosis and hip osteoarthritis. Management of osteopetrosis-related orthopedic problems is a surgical challenge due to increased bone density. Read More

Sci Rep 2017 Jun 7;7(1):3012. Epub 2017 Jun 7.

Centre for Bone and Arthritis Research, Department of internal medicine and clinical nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 405 30, Gothenburg, Sweden.

Autosomal recessive osteopetrosis (ARO) is a heterogeneous disorder, characterized by defective osteoclastic resorption of bone that results in increased bone density. We have studied nine individuals with an intermediate form of ARO, from the county of Västerbotten in Northern Sweden. All afflicted individuals had an onset in early infancy with optic atrophy, and in four patients anemia was present at diagnosis. Read More

Cell Rep 2017 Jun;19(10):2014-2025

Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address:

It is unknown whether and how very-low density lipoprotein receptors (VLDLRs) impact skeletal homeostasis. Here, we report that maternal and offspring VLDLRs play opposite roles in osteoclastogenesis and bone resorption. VLDLR deletion in the offspring augments osteoclast differentiation by enhancing RANKL signaling, leading to osteoporosis. Read More

J Bone Miner Metab 2017 Jun 6. Epub 2017 Jun 6.

Department of Bone and Joint Disease, National Center for Geriatrics and Gerontology, 7-430 Morioka, Obu, Aichi, 474-8511, Japan.

Src knockout (KO) and RANKL KO mice both exhibit near complete osteopetrosis in terms of 3D-bone volume (BV) fraction by micro-CT, whereas the serum CTX concentration of Src KO is apparently normal and that of RANKL KO is 30% of wild-type (WT) despite the fact that they lack osteoclasts. By histomorphometry we found that, whereas eroded surface (ES) and osteoid surface (OS) are zero values in RANKL KO, they are indistinguishable from WT in Src KO; because of marked increase in bone surface (BS), ES/BS and OS/BS of Src KO are 30-40% of WT. While RANKL KO lack both osteoclasts and osteoblasts, Src KO reveal increased numbers of osteoclasts and indistinguishable numbers of osteoblasts compared with WT; again, on the basis of BS, N. Read More

Chin J Traumatol 2017 Jun 10;20(3):173-176. Epub 2017 May 10.

Department of Orthopaedic Surgery, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, 310009, China.

Osteopetrosis is an inherited disorder characterized by increased bone density and brittle bone quality. Degenerative changes often occur after the age of 40 in patients with osteopetrosis. Operative intervention is the primary treatment option if the clinical manifestation of secondary osteoarthritis is severe. Read More

CEN Case Rep 2016 May 8;5(1):108-112. Epub 2015 Dec 8.

Department of Medicine (38), College of Medicine, King Saud University, P.O. Box 2925, Riyadh, 11461, Kingdom of Saudi Arabia.

Carbonic anhydrase II (CAII) deficiency is an autosomal recessive disorder characterized by renal tubular acidosis, osteopetrosis, recurrent bone fractures, renal stones, growth failure, and mental retardation. Several cases have been reported in Saudi Arabia with homozygous mutations in CA2 consistent with a high degree of consanguinity. We report a case of carbonic anhydrase II deficiency with short stature, mixed renal tubular acidosis, recurrent bone fractures due to trivial trauma, recurrent renal stones and cerebral calcification. Read More

Endocrinol Diabetes Metab Case Rep 2017 21;2017. Epub 2017 Apr 21.

Department of Internal Medicine and Endocrine Section, Medical School and Hospital Universitário Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de JaneiroBrazil.

Osteopetrosis (OP) comprehends a rare group of conditions, presenting on radiographs increased bone density, deriving from irregularities in osteoclast differentiation or function. In the autosomal dominant osteopetrosis (ADO), some patients stay asymptomatic for some time, or only develop mild symptoms. The dental surgeon is often the first to presuppose the disease during routine imaging examinations, referring the patient to a specialized medical group. Read More

Genes Genomics 2017 3;39(5):461-471. Epub 2017 Mar 3.

Department of Animal Improvement, Institute of Genetics and Animal Breeding, Polish Academy of Sciences, Postępu 36A, Jastrzębiec, 05-552 Magdalenka, Poland.

The main purpose of present review is to describe and organize autosomal recessive disorders (arachnomelia, syndactylism, osteopetrosis, dwarfism, crooked tail syndrome, muscular hyperplasia, glycogen storage disease, protoporphyria), which occur among beef cattle, and methods that can be applied to detect these defects. Prevalence of adverse alleles in beef breeds happens due to human activity-selections of favorable features, e.g. Read More

Isr Med Assoc J 2017 Jan;19(1):65-66

Department of Medicine, School of Medicine, Nazarbayev University, Astana, Kazakhstan.

Malays Orthop J 2017 Mar;11(1):64-67

Department of Orthopaedics, Tan Tock Seng Hospital, Singapore.

The treatment of fractures in osteopetrosis can be complicated and difficult. We describe the use of an industrial grade tungsten carbide drill bit in the treatment of one of these complex fractures. An industrial grade tungsten carbide drill bit was used to fashion a medullary canal in the surgical treatment of a left peri-implant fracture of the neck of femur in a patient with osteopetrosis. Read More

BMJ Case Rep 2017 Apr 22;2017. Epub 2017 Apr 22.

Komoro Kosei General Hospital, Komoro, Japan.

N Engl J Med 2017 Apr;376(16):e34

MNR Dental College, Telangana, India

J Assoc Physicians India 2016 Dec;64(12):92-94

Assistant Professor, Dept. of Medicine, Midnapore Medical College, Midnapore, West Bengal.

Osteopetrosis is a rare disorder of osteoclastic bone resorption leading to hyperostosis. Albers-Schonberg disease, an autosomal dominant variant of osteopetrosis occurs in young adults and has a benign course. A 17 year old female presented with generalized weakness and pallor for last two months. Read More

Eur Spine J 2017 May 9;26(Suppl 1):229-235. Epub 2017 Apr 9.

Spine Fellow, Lilavati Hospital and Research Centre, Bandra reclamation, Bandra west, Mumbai, Maharashtra, 400050, India.

Study Design: Single case report.

Objective/purpose: To report multiple level fractures of cervical spine in a patient with osteopetrosis and its management. Osteopetrosis is a rare inherited condition characterized by defective remodeling resulting in hard and brittle bones with diffuse osteosclerosis. Read More

Front Pharmacol 2017 23;8:151. Epub 2017 Mar 23.

Department of Physiology and Biophysics, Dalhousie University, Halifax NS, Canada.

The discovery of ClC proteins at the beginning of the 1990s was important for the development of the Cl(-) transport research field. ClCs form a large family of proteins that mediate voltage-dependent transport of Cl(-) ions across cell membranes. They are expressed in both plasma and intracellular membranes of cells from almost all living organisms. Read More

Genet Med 2017 Apr 6. Epub 2017 Apr 6.

Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

Purpose: The purpose of this study is to describe recessive alleles in strictly dominant genes. Identifying recessive mutations in genes for which only dominant disease or risk alleles have been reported can expand our understanding of the medical relevance of these genes both phenotypically and mechanistically. The Saudi population is enriched for autozygosity, which enhances the homozygous occurrence of alleles, including pathogenic alleles in genes that have been associated only with a dominant inheritance pattern. Read More

Bone Res 2017 14;5:17003. Epub 2017 Mar 14.

Musculoskeletal Disease Center, Jerry L. Pettis Memorial VA Medical Center, Loma Linda, CA, USA; Department of Medicine, Loma Linda University, Loma Linda, CA, USA.

Leucine-rich repeat kinase 1 (LRRK1) plays a critical role in regulating cytoskeletal organization, osteoclast activity, and bone resorption with little effect on bone formation parameters. Deficiency of Lrrk1 in mice causes a severe osteopetrosis in the metaphysis of the long bones and vertebrae bones, which makes LRRK1 an attractive alternative drug target for the treatment of osteoporosis and other high-turnover bone diseases. This review summarizes recent advances on the functions of the Lrrk1-related family members, Lrrk1 deficiency-induced skeletal phenotypes, LRRK1 structure-function, potential biological substrates and interacting proteins, and the mechanisms of LRRK1 action in osteoclasts. Read More

J Cell Biochem 2017 Mar 11. Epub 2017 Mar 11.

Faculty of Dentistry, Dental Research Institute, University of Toronto, Toronto, Ontario, Canada.

Vacuolar H(+) -ATPases (V-ATPases) are ubiquitous multisubunit proton pumps responsible for organellar pH maintenance. Mutations in the a3 subunit of V-ATPases cause autosomal recessive osteopetrosis, a rare disease due to impaired bone resorption. Patients with osteopetrosis also display dental anomalies, such as enamel defects; however, it is not clear whether these enamel abnormalities are a direct consequence of the a3 mutations. Read More

Mil Med 2017 Mar;182(3):e1886-e1888

Division of Endocrinology, Department of Medicine, Naval Medical Center San Diego, 34800 Bob Wilson Drive, San Diego, CA 92134-3300.

Introduction: Osteopetrosis is a connective tissue disorder resulting from abnormally dense bone predisposing patients to fracture. The clinical pattern of fractures across time and space as well as suggestive radiographic findings usually raises diagnostic suspicion. Multiple genetic mutations resulting in dysfunctional osteoclasts have been implicated in the pathogenesis of osteopetrosis with variable inheritance patterns. Read More

Cell Mol Life Sci 2017 Jul 3;74(14):2569-2586. Epub 2017 Mar 3.

INSERM UMR1064, Center for Research in Transplantation and Immunology-ITUN, Université de Nantes, 30 Bd. Jean Monnet, 44093, Nantes Cedex 01, France.

Interleukin-34 is a cytokine with only partially understood functions, described for the first time in 2008. Although IL-34 shares very little homology with CSF-1 (CSF1, M-CSF), they share a common receptor CSF-1R (CSF-1R) and IL-34 has also two distinct receptors (PTP-ζ) and CD138 (syndecan-1). To make the situation more complex, IL-34 has also been shown as pairing with CSF-1 to form a heterodimer. Read More

Skeletal Radiol 2017 May 23;46(5):701-704. Epub 2017 Feb 23.

Department of Pediatrics, School of Medicine, Ondokuz Mayıs University, Kurupelit, Samsun, Turkey.

Osteopetrosis is a hereditary form of sclerosing bone dysplasia with various radiological and clinical presentations. The autosomal recessive type, also known as malignant osteopetrosis, is the most severe type, with the early onset of manifestations. A 5-month-old infant was admitted to our hospital with recurrent respiratory tract infections. Read More

J R Soc Interface 2017 Feb;14(127)

Department of Molecular Cell Biology, Weizmann Institute of Science, Wolfson Building for Biological Research, Room 618, 234 Herzl Street, 7610001 Rehovot, Israel

Bone homeostasis is continuously regulated by the coordinated action of bone-resorbing osteoclasts and bone-forming osteoblasts. Imbalance between these two cell populations leads to pathological bone diseases such as osteoporosis and osteopetrosis. Osteoclast functionality relies on the formation of sealing zone (SZ) rings that define the resorption lacuna. Read More

Indian J Dent Res 2016 Nov-Dec;27(6):667-671

Department of Oral Medicine and Radiology, Tamil Nadu Government Dental College and Hospital, Chennai, Tamil Nadu, India.

Osteopetrosis is a rare genetic bone disorder arising due to a defect in the differentiation or function of osteoclast which results in a generalized increase in bone mass. Osteomyelitis is one of the most common complications because of decreased bone marrow function and compromised blood supply. Radiologist plays a vital role in diagnosing osteopetrosis. Read More

Bone 2017 Feb 4. Epub 2017 Feb 4.

Department of Medicine, Indiana University, 1120 W. Michigan St., Indianapolis, IN 46202, USA; Department of Medical and Molecular Genetics, Indiana University, 1120 W. Michigan St., Indianapolis, IN 46202, USA. Electronic address:

Osteopetroses are a heterogeneous group of rare genetic bone diseases sharing the common hallmarks of reduced osteoclast activity, increased bone mass and high bone fragility. Osteoclasts are bone resorbing cells that contribute to bone growth and renewal through the erosion of the mineralized matrix. Alongside the bone forming activity by osteoblasts, osteoclasts allow the skeleton to grow harmonically and maintain a healthy balance between bone resorption and formation. Read More

Bone 2017 Jan 20. Epub 2017 Jan 20.

Division of Endocrinology and Metabolism and the Institute for Human Genetics, Department of Medicine, University of California, San Francisco, CA, United States.

A working group on rare bone diseases was held in Atlanta, Georgia as part of the 2016 annual meeting of the American Society for Bone and Mineral Research. The meeting was organized by Matthew Drake. Given recent advances in our understanding of fibrodysplasia ossificans progressiva (FOP), the initial portion of the program was devoted to basic, translational, and clinical aspects of FOP. Read More

Stem Cells 2017 May 1;35(5):1365-1377. Epub 2017 Mar 1.

Milan Unit, CNR-IRGB, Milan, Italy.

Autosomal recessive osteopetrosis (ARO) is a severe bone disease characterized by increased bone density due to impairment in osteoclast resorptive function or differentiation. Hematopoietic stem cell transplantation is the only available treatment; however, this therapy is not effective in RANKL-dependent ARO, since in bone this gene is mainly expressed by cells of mesenchymal origin. Of note, whether lack of RANKL production might cause a defect also in the bone marrow (BM) stromal compartment, possibly contributing to the pathology, is unknown. Read More

Bone 2017 Apr 14;97:126-129. Epub 2017 Jan 14.

Humanitas Clinical and Research Institute, Rozzano, Italy; CNR-IRGB, Milan Unit, Milan, Italy.

Osteopetrosis (OPT) is a rare skeletal disorder with phenotypic and genotypic heterogeneity: a variety of clinical features besides the bony defect may be present, and at least ten different genes are known to be involved in the disease pathogenesis. In the framework of this heterogeneity, we report the clinical description of a neonate, first child of consanguineous parents, who had osteoclast-rich osteopetrosis and bone marrow failure in early life, but no other usual classical features of infantile malignant OPT, such as visual or hearing impairments. Because of the severe presentation at birth, the patient received Hematopoietic Stem Cell Transplantation (HSCT) at 2months of age with successful outcome. Read More

Front Vet Sci 2016 15;3:113. Epub 2016 Dec 15.

National Animal Disease Center, USDA, ARS , Ames, IA , USA.

There are genetic conditions that influence production in dairy and beef cattle. The objective of this review was to describe relevant genetic conditions that have been associated with productivity and health in cattle. Genes or genomic regions that have been identified as a candidate for the condition will be included, and the genetic basis of the condition will be defined. Read More

J Craniofac Surg 2016 Nov;27(8):e728-e730

Department of Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, Liaoning Institute of Dental Research, Heping District, Shenyang, China.

Osteopetrosis represents a heterogeneous group of rare, hereditary bone disorders with variable clinical features, and an increase in bone density. Osteomyelitis of the jaws is a significant complication of osteopetrosis. In this article, a reported patient with osteopetrosis complicated by osteomyelitis of the mandible was examined. Read More

Bone Res 2016 29;4:16035. Epub 2016 Nov 29.

Laboratory of Endocrinology and Metabolism, Department of Endocrinology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University , Chengdu, China.

Type II autosomal dominant osteopetrosis (ADO2), which is the most common form of osteopetrosis, is caused by heterozygous mutations in the chloride channel 7 (CLCN7) gene. The osteopetrosis of ADO2 has been attributed to hypofunctional osteoclasts. The mechanism underlying the abnormality in osteoclast function remains largely unknown. Read More

Pediatr Rev 2016 Dec;37(12):539-541

Division of Paediatric Hematology/Oncology, Department of Paediatrics, IWK Health Centre, Dalhousie University, Halifax, Nova Scotia, Canada.

Intractable Rare Dis Res 2016 Nov;5(4):284-289

Paediatric Nephrology Unit, Department of Pediatrics, Nuestra Señora de Candelaria University Hospital, Tenerife, Spain.

Sclerosing bone dysplasias are a series of clinically and genetically heterogeneous diseases characterized by functional failure of the osteoclasts in bone resorption, leading to an excessive amount of bone mineral density (BMD) which could have serious clinical consequences. We treated three children affected with seriously high levels of BMD with acetazolamide, with the intention of inducing metabolic acidosis, thus increasing bone resorption and reducing BMD. All our patients tolerated and followed the treatment well and the clinical response was satisfactory in all cases. Read More

Am J Hum Genet 2016 Dec 23;99(6):1388-1394. Epub 2016 Nov 23.

Ophthalmic Genetics and Visual Function Branch, National Eye Institute, NIH, Bethesda, MD 20892, USA; Children's National Medical Center, Washington, DC 20010, USA. Electronic address:

Human MITF is, by convention, called the "microphthalmia-associated transcription factor" because of previously published seminal mouse genetic studies; however, mutations in MITF have never been associated with microphthalmia in humans. Here, we describe a syndrome that we term COMMAD, characterized by coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness. COMMAD is associated with biallelic MITF mutant alleles and hence suggests a role for MITF in regulating processes such as optic-fissure closure and bone development or homeostasis, which go beyond what is usually seen in individuals carrying monoallelic MITF mutations. Read More

Exp Ther Med 2016 Nov 15;12(5):2811-2814. Epub 2016 Sep 15.

Department of Otorhinolaryngology, Xiamen Chang Gung Hospital, Xiamen, Fujian 361000, P.R. China.

Osteopetrosis is a rare bone disease caused by metabolic imbalances as a result of genetic mutations. For instance, autosomal dominant osteopetrosis is caused by a missense mutation of the C1CN7 gene. This was first reported in 1904 and is thought to be caused by osteoclastic dysfunction and an impaired bone resorption ability. Read More

J Bone Miner Res 2017 Apr 14;32(4):757-769. Epub 2016 Dec 14.

Center for Metabolic Bone Disease and Molecular Research, Shriners Hospital for Children, St. Louis, MO, USA.

In 1985, we briefly reported infant sisters with a unique, lethal, autosomal recessive disorder designated congenital sclerosing osteomalacia with cerebral calcification. In 1986, this condition was entered into Mendelian Inheritance In Man (MIM) as osteomalacia, sclerosing, with cerebral calcification (MIM 259660). However, no attestations followed. Read More

Eur Arch Paediatr Dent 2016 Dec 17;17(6):435-443. Epub 2016 Nov 17.

Dept of Oral Health Sciences-Orthodontics, University Hospitals Leuven, KU Leuven and Dentistry, Kapucijnenvoer 7, 3000, Louvain, Belgium.

Aim: To describe dental and dentofacial characteristics observed in patients diagnosed with osteopetrosis and to advise a dental care approach in these patients.

Methods: Four patients were clinically diagnosed with osteopetrosis, characterised by increased bone density, bone marrow failure, blindness and deafness due to compression of cranial nerves. All patients were dentally screened at different ages (2. Read More

Neurochirurgie 2016 Dec 14;62(6):300-305. Epub 2016 Nov 14.

Service de neurochirurgie pédiatrique, hôpital Necker-Enfants-Malades, AP-HP, 149, rue de Sèvres, 75743 Paris cedex 15, France.

Suprasellar arachnoid cysts (SAC) in children are considered rare, but the incidence is increasing due to the improvement of prenatal diagnosis. We present 15 cases of SAC diagnosed during the antenatal period between 2005 and 2015. The records were reviewed retrospectively by specifying the radiological characteristics, treatment modalities, outcomes, and long-term monitoring. Read More

Int Med Case Rep J 2016 1;9:347-351. Epub 2016 Nov 1.

Department of Trauma and Orthopedics, Adana Numune Training and Educational Hospital, Adana, Turkey.

Osteopetrosis is a rare, inherited disease characterized by defects in osteoclastic function that results in defective bone resorption. When fractures are encountered, fixation is extremely difficult. Osteopetrosis patients have an increased predisposition to infection. Read More

Clin Genet 2017 Jun 19;91(6):902-907. Epub 2017 Mar 19.

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Mutations of several genes have been implicated in autosomal recessive osteopetrosis (OP), a disease caused by impaired function and differentiation of osteoclasts. Severe combined immune deficiencies (SCID) can likewise result from different genetic mutations. We report two siblings with SCID and an atypical phenotype of OP. Read More

Bone 2017 Jan 14;94:34-41. Epub 2016 Oct 14.

Medicine, Indiana University School of Medicine, IN, USA; Medical and Molecular Genetics, Indiana University School of Medicine, IN, USA.

Autosomal dominant osteopetrosis type II (ADO2) is a heritable osteosclerotic bone disorder due to dysfunctional osteoclast activity. ADO2 is caused by missense mutations in the chloride channel 7 (CLCN7) gene characterized by osteosclerosis with multiple fractures. ADO2 can result in osteomyelitis, visual loss and bone marrow failure. Read More

Bone Marrow Transplant 2016 Nov 4;51(11):1546-1548. Epub 2016 Jul 4.

Department of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN, USA.

J Biotechnol 2016 Dec 27;240:48-60. Epub 2016 Oct 27.

College of Science and Engineering, James Cook University, Townsville 4811, Queensland, Australia; Centre for Biodiscovery and Molecular Development of Therapeutics, James Cook University, Townsville 4811, Queensland, Australia. Electronic address:

Human interferon gamma is a cytokine belonging to a diverse group of interferons which have a crucial immunological function against mycobacteria and a wide variety of viral infections. To date, it has been approved for treatment of chronic granulomatous disease and malignant osteopetrosis, and its application as an immunotherapeutic agent against cancer is an increasing prospect. Recombinant human interferon gamma, as a lucrative biopharmaceutical, has been engineered in different expression systems including prokaryotic, protozoan, fungal (yeasts), plant, insect and mammalian cells. Read More

JCI Insight 2016 Oct 20;1(17):e86330. Epub 2016 Oct 20.

Center for Osteoporosis and Metabolic Bone Diseases, Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.; Department of Physiology and Biophysics, and.

Mutations of the Plekhm1 gene in humans and rats cause osteopetrosis, an inherited bone disease characterized by diminished bone resorption by osteoclasts. PLEKHM1 binds to RAB7 and is critical for lysosome trafficking. However, the molecular mechanisms by which PLEKHM1 regulates lysosomal pathways remain unknown. Read More

J Cell Physiol 2017 Sep 12;232(9):2538-2549. Epub 2017 Apr 12.

Division of Allergy/Immunology and Rheumatology, The University of Rochester, Rochester, New York.

DC-STAMP is a multi-pass transmembrane protein essential for cell-cell fusion between osteoclast precursors during osteoclast (OC) development. DC-STAMP-/- mice have mild osteopetrosis and form mononuclear cells with limited resorption capacity. The identification of an Immunoreceptor Tyrosine-based Inhibitory Motif (ITIM) on the cytoplasmic tail of DC-STAMP suggested a potential signaling function. Read More

Bonekey Rep 2016 21;5:839. Epub 2016 Sep 21.

Department of Oral and Craniofacial Sciences, University of Missouri-Kansas City School of Dentistry , Kansas City, MO, USA.

Rare bone diseases, generally defined as monogenic traits with either autosomal recessive or dominant patterns of inheritance, have provided a rich database of genes and associated pathways over the past 2-3 decades. The molecular genetic dissection of these bone diseases has yielded some major surprises in terms of the causal genes and/or involved pathways. The discovery of genes/pathways involved in diseases such as osteopetrosis, osteosclerosis, osteogenesis imperfecta and many other rare bone diseases have all accelerated our understanding of complex traits. Read More

Aust Vet J 2016 Oct;94(10):358-61

Faculty of Veterinary Science, University of Melbourne, Melbourne, Victoria, Australia.

Osteopetrosis is a rare disorder characterised by a defect in osteoclastic bone resorption. This report describes osteopetrosis in a neonatal donkey that suffered a displaced tibial fracture. Radiographic examination identified generalised reduction in medullary cavity size, thickened mid-diaphyseal cortices and conical metaphyseal bone extending toward the mid-diaphysis of long bones. Read More