To evaluate the efficacy and safety of aromatase inhibitor letrozole in treatment of male adolescents with idiopathic short stature (ISS). Seventy five boys with height less than 2 standard deviation (SD) below the mean who had entered puberty were enrolled in our study from 2004 to 2017, in the Pediatric Department of the First Affiliated Hospital, Sun Yat-Sen University. Among 75 patients, 28 in letrozole group received letrozole and spironolactone, 30 in gonadotrophin releasing hormone analogue (GnRHa) group received GnRHa injection and 17 had no intervention. Height velocity (HV), increment of bone age/chronological age (ΔBA/ΔCA), the final adult height (FAH) were compared among groups and the safety of letrozole treatment was evaluated. HV maintained faster during letrozole treatment when compared with other groups. HV during GnRHa treatment showed slightly decline in the first 6 months, but decreased remarkably after 6 months, and was significantly lower than that in letrozole group ( < 0.05). The maturation of BA slowed down in both letrozole and GnRHa groups. But the ΔBA/ΔCA in letrozole group during the first and the second year of treatment were significantly higher (0.67±0.09, 0.50±0.15, respectively) when compared with GnRHa group (0.59±0.16, 0.44±0.13, respectively) ( =2.78 and 2.20, all < 0.05). FAH in letrozole group and GnRHa group were (170±4) cm and (170±6)cm, there was no significant differences between the two groups ( >0.05), and both were higher than that in no intervention group (162±4 cm, < 0.01). After 6 months of letrozole treatment, testicular volumes and serum testerone levels increased; 39.2% (11/28) boys had clinical manifestations of hyperandrogenemia, and 82.1% (23/28) boys had decreased serum high-density lipoprotein (HDL) levels. Serum levels of HDL and testerone returned normal and the hyperandrogenemia disappeared after the cessation of letrozole treatment. No significant changes in serum triglyceride, serum low-density lipoprotein (LDL), fating serum levels of insulin and glucose, HOMA-IR were observed. No abnormal liver function, myalgia, scoliosis or aggravations of scoliosis was found. Long term letrozole therapy during puberty in boys with ISS can delay bone maturation without significant decrease of linear growth, and thus can improve the final adult height. No severe adverse reactions were found.
Adolescent ; Body Height ; Bone Development ; Child ; Gonadotropin-Releasing Hormone ; Growth Disorders ; Humans ; Letrozole ; therapeutic use ; Male

After the articular cartilage injury, the metabolic level is increased during the progressive degeneration, the chondrocytes secrete a variety of inflammatory factors, and the original cell phenotype is gradually changed. For a long time, a large number of researchers have done a lot of researches to promote anabolism of chondrocytes and to maintain the stability of chondrocyte phenotype. There are many molecular signaling pathways involved in the process of promoting cartilage repair. This review focuses on the key signaling molecules in articular cartilage repair, such as transforming growth factor-beta and bone morphogenetic protein, and reveals their roles in the process of cartilage injury and repair, so that researchers in related fields can understand the molecular mechanism of cartilage injury and repair widely and deeply. Based on this, they may find promising targets and biological methods for the treatment of cartilage injury.
Bone Morphogenetic Proteins ; physiology ; Cartilage, Articular ; growth & development ; injuries ; Chondrocytes ; physiology ; Humans ; Regeneration ; Signal Transduction ; Transforming Growth Factor beta ; physiology

BACKGROUND: For the bone-specific imaging, a structure-inherent targeting of bone tissue recently has been reported a new strategy based on incorporation of targeting moieties into the chemical structure of near-infrared (NIR) contrast agents, while conventional methods require covalent conjugation of bone-targeting ligands to NIR contrast agents. This will be a new approach for bone-targeted imaging by using the bifunctional NIR contrast agents. METHODS: The goal of this review is to provide an overview of the recent advances in optical imaging of bone tissue, highlighting the structure-inherent targeting by developing NIR contrast agents without the need for a bone-targeting ligand such as bisphosphonates. RESULTS: A series of iminodiacetated and phosphonated NIR contrast agents for the structure-inherent targeting of bone tissue showed excellent bone-targeting ability in vivo without non-specific binding. Additionally, the phosphonated NIR contrast agents could be useful in the diagnosis of bone metastasis. CONCLUSION: By developing bone-targeted NIR contrast agents, optical imaging of bone tissue makes it very attractive for preclinical studies of bone growth or real-time fluorescence guided surgery resulting in high potential to shift the clinical paradigms.
Bone and Bones ; Bone Development ; Contrast Media ; Diagnosis ; Diphosphonates ; Fluorescence ; Ligands ; Neoplasm Metastasis ; Optical Imaging ; Surgery, Computer-Assisted

Jugular bulb diverticulum is an irregular extension of the jugular bulb into the temporal bone that may be symptomatic or asymptomatic. The jugular bulb has rarely been reported to extend into the occipital condyle; such extension is termed a condylar jugular diverticulum and is characterized as a defect in the occipital condyle contiguous with the jugular bulb. This report details 3 cases of condylar jugular diverticulum. Extension of the jugular bulb into the ipsilateral occipital condyle was noted as an incidental finding on cone-beam computed tomographic (CBCT) images of 3 patients. All 3 patients were asymptomatic, and this finding was unrelated to the initial area of interest. CBCT use is becoming ubiquitous in dentistry, as it allows 3-dimensional evaluation, unlike conventional radiography. Proper interpretation of the entire CBCT is essential, and recognition of the indicators of condylar jugular diverticulum may prevent misdiagnosis of this rare entity.
Cone-Beam Computed Tomography ; Dentistry ; Diagnostic Errors ; Diverticulum ; Growth and Development ; Humans ; Incidental Findings ; Jugular Veins ; Radiography ; Temporal Bone

PURPOSE: The modified minimally invasive surgical technique (M-MIST) has been successfully employed to achieve periodontal regeneration. Platelet-rich fibrin (PRF) is known to enhance wound healing through the release of growth factors. This study aimed to observe the outcomes of periodontal surgery when M-MIST was used with or without PRF for the treatment of isolated intrabony defects.METHODS: This randomized clinical trial was conducted on 36 systemically healthy patients, who had chronic periodontitis associated with a single-site buccal probing pocket depth (PPD) and clinical attachment level of ≥5 mm. Patients were randomly divided into 2 groups: the test group treated with M-MIST and PRF, and the control group treated with M-MIST alone. The primary periodontal parameters analyzed were PPD, relative attachment level (RAL), and relative gingival margin level. The radiographic parameters analyzed were change in alveolar crest position (C-ACP), linear bone growth (LBG), and percentage bone fill (%BF). Patients were followed up to 6 months post-surgery.RESULTS: Intragroup comparisons at 3 and 6 months showed consistently significant improvements in PPD and RAL in both the groups. In intergroup comparisons, the improvement in PPD reduction, gain in RAL, and the level of the gingival margin was similar in both groups at 3 and 6 months of follow-up. Furthermore, an intergroup comparison of radiographic parameters also demonstrated similar improvements in C-ACP, LBG, and %BF at 6 months of follow-up.CONCLUSIONS: M-MIST with or without PRF yielded comparable periodontal tissue healing in terms of improvements in periodontal and radiographic parameters. Further investigation is required to confirm the beneficial effects of PRF with M-MIST.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03169920
Bone Development ; Chronic Periodontitis ; Fibrin ; Follow-Up Studies ; Humans ; Intercellular Signaling Peptides and Proteins ; Microsurgery ; Minimally Invasive Surgical Procedures ; Regeneration ; Wound Healing

Wnt/β-catenin signaling plays a critical role in the achievement of peak bone mass, affecting the commitment of mesenchymal progenitors to the osteoblast lineage and the anabolic capacity of osteoblasts depositing bone matrix. Recent studies suggest that this evolutionarily-conserved, developmental pathway exerts its anabolic effects in part by coordinating osteoblast activity with intermediary metabolism. These findings are compatible with the cloning of the gene encoding the low-density lipoprotein related receptor-5 (LRP5) Wnt co-receptor from a diabetes-susceptibility locus and the now well-established linkage between Wnt signaling and metabolism. In this article, we provide an overview of the role of Wnt signaling in whole-body metabolism and review the literature regarding the impact of Wnt signaling on the osteoblast's utilization of three different energy sources: fatty acids, glucose, and glutamine. Special attention is devoted to the net effect of nutrient utilization and the mode of regulation by Wnt signaling. Mechanistic studies indicate that the utilization of each substrate is governed by a unique mechanism of control with β-catenin-dependent signaling regulating fatty acid β-oxidation, while glucose and glutamine utilization are β-catenin-independent and downstream of mammalian target of rapamycin complex 2 (mTORC2) and mammalian target of rapamycin complex 1 (mTORC1) activation, respectively. The emergence of these data has provided a new context for the mechanisms by which Wnt signaling influences bone development.
Anabolic Agents ; beta Catenin ; Bone Development ; Bone Matrix ; Clone Cells ; Cloning, Organism ; Fatty Acids ; Glucose ; Glutamine ; Lipoproteins ; Metabolism* ; Osteoblasts* ; Sirolimus

BACKGROUND: The objective of this study was to evaluate the influence of masticatory muscle injection of botulinum toxin type A (BTX-A) on the growth of the mandibular bone in vivo. METHODS: Eleven Sprague-Dawley rats were used, and BTX-A (n = 6) or saline (n = 5) was injected at 13 days of age. All injections were given to the right masseter muscle, and the BTX-A dose was 0.5 units. All of the rats were euthanized at 60 days of age. The skulls of the rats were separated and fixed with 10% formalin for micro-computed tomography (micro-CT) analysis. RESULTS: The anthropometric analysis found that the ramus heights and bigonial widths of the BTX-A-injected group were significantly smaller than those of the saline-injected group (P < 0.05), and the mandibular plane angle of the BTX-A-injected group was significantly greater than in the saline-injected group (P < 0.001). In the BTX-A-injected group, the ramus heights II and III and the mandibular plane angles I and II showed significant differences between the injected and non-injected sides (P < 0.05). The BTX-A-injected side of the mandible in the masseter group showed significantly lower mandibular bone growth compared with the non-injected side. CONCLUSION: BTX-A injection into the masseter muscle influences mandibular bone growth.
Animals ; Bone Development ; Botulinum Toxins ; Botulinum Toxins, Type A ; Formaldehyde ; Mandible ; Masseter Muscle ; Masticatory Muscles ; Rats ; Rats, Sprague-Dawley ; Skull

Platyspondylic lethal skeletal dysplasia, Torrance type (PLSD-T), is one of the phenotypes of type II collagenopathy and is characteristic of severe bone growth disorder. This phenotype may limit the growth and expansion of the lungs, which is known to cause death from respiratory failure during or shortly after birth, but in few less severe cases, patients have been reported to have survived to adulthood. We have experienced a case of PLSD-T in a preterm infant who was delivered via cesarean section at the gestational age of 29 weeks 3 days, with a birth weight of 1.15 kg. Physical examination of the infant revealed characteristic findings of short arms and legs, small thorax, distended abdomen, and cleft palate. On the basis of the subsequent genetic testing, the patient had a heterozygous mutation in the encoded c-propeptide region of collagen, type II, alpha 1 (COL2A1), c.4335G>A (p.Trp1445*) in exon 52. This is the first case of PLSD-T diagnosed in Korea, and we hereby report the case.
Abdomen ; Arm ; Birth Weight ; Bone Development ; Cesarean Section ; Cleft Palate ; Collagen Type II ; Exons ; Female ; Genetic Testing ; Gestational Age ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Korea ; Leg ; Lung ; Parturition ; Phenotype ; Physical Examination ; Pregnancy ; Respiratory Insufficiency ; Thorax

OBJECTIVES: Current treatments for osteoporosis were prevention of progression, yet it has been questionable in the stimulation of bone growth. The mesenchymal stem cells (MSCs) treatment for osteoporosis aims to induce differentiation of bone progenitor cells into bone-forming osteoblasts. We investigate whether human umbilical cord blood (hUCB)-MSCs transplantation may induce bone regeneration for osteoporotic rat model induced by ovariectomy. METHODS: The ovariectomized (OVX) group (n = 10) and OVX-MSCs group (n = 10) underwent bilateral ovariectomy to induce osteoporosis, while the Sham group (n = 10) underwent sham operation at aged 12 weeks. After a femoral defect was made at 9 months, Sham group and OVX group were injected with Hartmann solution, while the OVX-MSCs group was injected with Hartmann solution containing 1 × 107 hUCB-MSCs. The volume of regenerated bone was evaluated using micro-computed tomography at 4 and 8 weeks postoperation. RESULTS: At 4- and 8-week postoperation, the OVX group (5.0% ± 1.5%; 6.1% ± 0.7%) had a significantly lower regenerated bone volume than the Sham group (8.6% ± 1.3%; 12.0% ± 1.8%, P < 0.01), respectively. However, there was no significant difference between the OVX-MSCs and Sham groups. The OVX-MSCs group resulted in about 53% and 65% significantly higher new bone formation than the OVX group (7.7% ± 1.9%; 10.0% ± 2.9%, P < 0.05). CONCLUSIONS: hUCB-MSCs in bone defects may enhance bone regeneration in osteoporotic rat model similar to nonosteoporotic bone regeneration. hUCB-MSCs may be a promising alternative stem cell therapy for osteoporosis.
Animals ; Bone Development ; Bone Regeneration ; Female ; Fetal Blood ; Humans ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; Models, Animal ; Osteoblasts ; Osteogenesis ; Osteoporosis ; Ovariectomy ; Rats ; Stem Cells ; Umbilical Cord

The bone morphogenetic protein (BMP) family is an important factor in the regulation of cell ular life activities and in the development of almost all tissues. BMP-mediated signaling plays an important role in tooth root development, which is a part of tooth development. Epithelial and mesenchymal interactions are involved in tooth root development, but the BMP signaling pathway has a different effect on tooth root development in epithelial and mesenchymal. This review summarizes the advances of BMP signaling in tooth root development.
Bone Morphogenetic Protein 2 ; Bone Morphogenetic Protein 7 ; Bone Morphogenetic Proteins ; physiology ; Odontogenesis ; Signal Transduction ; Tooth ; Tooth Root ; growth & development