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Physiological Reviews Oct 2018Bone morphogenetic proteins (BMPs) constitute the largest subdivision of the transforming growth factor-β family of ligands. BMPs exhibit widespread utility and... (Review)
Review
Bone morphogenetic proteins (BMPs) constitute the largest subdivision of the transforming growth factor-β family of ligands. BMPs exhibit widespread utility and pleiotropic, context-dependent effects, and the strength and duration of BMP pathway signaling is tightly regulated at numerous levels via mechanisms operating both inside and outside the cell. Defects in the BMP pathway or its regulation underlie multiple human diseases of different organ systems. Yet much remains to be discovered about the BMP pathway in its original context, i.e., the skeleton. In this review, we provide a comprehensive overview of the intricacies of the BMP pathway and its inhibitors in bone development, homeostasis, and disease. We frame the content of the review around major unanswered questions for which incomplete evidence is available. First, we consider the gene regulatory network downstream of BMP signaling in osteoblastogenesis. Next, we examine why some BMP ligands are more osteogenic than others and what factors limit BMP signaling during osteoblastogenesis. Then we consider whether specific BMP pathway components are required for normal skeletal development, and if the pathway exerts endogenous effects in the aging skeleton. Finally, we propose two major areas of need of future study by the field: greater resolution of the gene regulatory network downstream of BMP signaling in the skeleton, and an expanded repertoire of reagents to reliably and specifically inhibit individual BMP pathway components.
Topics: Animals; Bone Morphogenetic Proteins; Gene Expression Regulation; Humans; Osteogenesis; Signal Transduction; Skeleton
PubMed: 30156494
DOI: 10.1152/physrev.00028.2017 -
Aesthetic Plastic Surgery Aug 2012In principle, to achieve the most natural and harmonious rejuvenation of the face, all changes that result from the aging process should be corrected. Traditionally,... (Review)
Review
UNLABELLED
In principle, to achieve the most natural and harmonious rejuvenation of the face, all changes that result from the aging process should be corrected. Traditionally, soft tissue lifting and redraping have constituted the cornerstone of most facial rejuvenation procedures. Changes in the facial skeleton that occur with aging and their impact on facial appearance have not been well appreciated. Accordingly, failure to address changes in the skeletal foundation of the face may limit the potential benefit of any rejuvenation procedure. Correction of the skeletal framework is increasingly viewed as the new frontier in facial rejuvenation. It currently is clear that certain areas of the facial skeleton undergo resorption with aging. Areas with a strong predisposition to resorption include the midface skeleton, particularly the maxilla including the pyriform region of the nose, the superomedial and inferolateral aspects of the orbital rim, and the prejowl area of the mandible. These areas resorb in a specific and predictable manner with aging. The resultant deficiencies of the skeletal foundation contribute to the stigmata of the aging face. In patients with a congenitally weak skeletal structure, the skeleton may be the primary cause for the manifestations of premature aging. These areas should be specifically examined in patients undergoing facial rejuvenation and addressed to obtain superior aesthetic results.
LEVEL OF EVIDENCE IV
This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
Topics: Adult; Aging; Cheek; Facial Bones; Humans; Middle Aged; Nose; Orbit; Prostheses and Implants; Prosthesis Implantation; Plastic Surgery Procedures; Rejuvenation; Zygoma
PubMed: 22580543
DOI: 10.1007/s00266-012-9904-3 -
Physiological Reviews Jul 2018It is from the discovery of leptin and the central nervous system as a regulator of bone remodeling that the presence of autonomic nerves within the skeleton... (Review)
Review
It is from the discovery of leptin and the central nervous system as a regulator of bone remodeling that the presence of autonomic nerves within the skeleton transitioned from a mere histological observation to the mechanism whereby neurons of the central nervous system communicate with cells of the bone microenvironment and regulate bone homeostasis. This shift in paradigm sparked new preclinical and clinical investigations aimed at defining the contribution of sympathetic, parasympathetic, and sensory nerves to the process of bone development, bone mass accrual, bone remodeling, and cancer metastasis. The aim of this article is to review the data that led to the current understanding of the interactions between the autonomic and skeletal systems and to present a critical appraisal of the literature, bringing forth a schema that can put into physiological and clinical context the main genetic and pharmacological observations pointing to the existence of an autonomic control of skeletal homeostasis. The different types of nerves found in the skeleton, their functional interactions with bone cells, their impact on bone development, bone mass accrual and remodeling, and the possible clinical or pathophysiological relevance of these findings are discussed.
Topics: Adaptation, Physiological; Animals; Autonomic Nervous System; Bone Development; Bone Diseases; Bone Remodeling; Bone and Bones; Humans; Weight-Bearing
PubMed: 29717928
DOI: 10.1152/physrev.00014.2017 -
The Angle Orthodontist Aug 2002The present study aimed to provide a version of the Cervical Vertebral Maturation (CVM) method for the detection of the peak in mandibular growth based on the analysis...
The present study aimed to provide a version of the Cervical Vertebral Maturation (CVM) method for the detection of the peak in mandibular growth based on the analysis of the second through fourth cervical vertebrae in a single cephalogram. The morphology of the bodies of the second (odontoid process, C2), third (C3), and fourth (C4) cervical vertebrae were analyzed in six consecutive cephalometric observations (T1 through T6) of 30 orthodontically untreated subjects. Observations for each subject consisted of two consecutive cephalograms comprising the interval of maximum mandibular growth (as assessed by means of the maximum increment in total mandibular length, Co-Gn), together with two earlier consecutive cephalograms and two later consecutive cephalograms. The analysis consisted of both visual and cephalometric appraisals of morphological characteristics of the three cervical vertebrae. The construction of the new version of the CVM method was based on the results of both ANOVA for repeated measures with post-hoc Scheffé's test (P < .05) and discriminant analysis. The new CVM method presents with five maturational stages (Cervical Vertebral Maturation Stage [CVMS] I through CVMS V, instead of Cvs 1 through Cvs 6 in the former CVM method). The peak in mandibular growth occurs between CVMS II and CVMS III, and it has not been reached without the attainment of both CVMS I and CVMS II. CVMS V is recorded at least two years after the peak. The advantages of the new version of the CVM method are that mandibular skeletal maturity can be appraised on a single cephalogram and through the analysis of only the second, third, and fourth cervical vertebrae, which usually are visible even when a protective radiation collar is worn.
Topics: Adolescent; Age Determination by Skeleton; Analysis of Variance; Axis, Cervical Vertebra; Cephalometry; Cervical Vertebrae; Chi-Square Distribution; Child; Discriminant Analysis; Female; Follow-Up Studies; Humans; Longitudinal Studies; Male; Mandible; Multivariate Analysis; Odontoid Process; Statistics as Topic
PubMed: 12169031
DOI: 10.1043/0003-3219(2002)072<0316:AIVOTC>2.0.CO;2 -
Science (New York, N.Y.) Jul 2023The human skeletal form underlies bipedalism, but the genetic basis of skeletal proportions (SPs) is not well characterized. We applied deep-learning models to 31,221...
The human skeletal form underlies bipedalism, but the genetic basis of skeletal proportions (SPs) is not well characterized. We applied deep-learning models to 31,221 x-rays from the UK Biobank to extract a comprehensive set of SPs, which were associated with 145 independent loci genome-wide. Structural equation modeling suggested that limb proportions exhibited strong genetic sharing but were independent of width and torso proportions. Polygenic score analysis identified specific associations between osteoarthritis and hip and knee SPs. In contrast to other traits, SP loci were enriched in human accelerated regions and in regulatory elements of genes that are differentially expressed between humans and great apes. Combined, our work identifies specific genetic variants that affect the skeletal form and ties a major evolutionary facet of human anatomical change to pathogenesis.
Topics: Humans; Genome-Wide Association Study; Multifactorial Inheritance; Phenotype; Polymorphism, Single Nucleotide; Genome, Human; Skeleton; Evolution, Molecular; Male; Female
PubMed: 37471560
DOI: 10.1126/science.adf8009 -
The Angle Orthodontist Mar 2018The cervical vertebral maturation (CVM) method is used to determine the craniofacial skeletal maturational stage of an individual at a specific time point during the...
The cervical vertebral maturation (CVM) method is used to determine the craniofacial skeletal maturational stage of an individual at a specific time point during the growth process. This diagnostic approach uses data derived from the second (C2), third (C3), and fourth (C4) cervical vertebrae, as visualized in a two-dimensional lateral cephalogram. Six maturational stages of those three cervical vertebrae can be determined, based on the morphology of their bodies. The first step is to evaluate the inferior border of these vertebral bodies, determining whether they are flat or concave (ie, presence of a visible notch). The second step in the analysis is to evaluate the shape of C3 and C4. These vertebral bodies change in shape in a typical sequence, progressing from trapezoidal to rectangular horizontal, to square, and to rectangular vertical. Typically, cervical stages (CSs) 1 and CS 2 are considered prepubertal, CS 3 and CS 4 circumpubertal, and CS 5 and CS 6 postpubertal. Criticism has been rendered as to the reproducibility of the CVM method. Diminished reliability may be observed at least in part due to the lack of a definitive description of the staging procedure in the literature. Based on the now nearly 20 years of experience in staging cervical vertebrae, this article was prepared as a "user's guide" that describes the CVM stages in detail in attempt to help the reader use this approach in everyday clinical practice.
Topics: Age Determination by Skeleton; Cervical Vertebrae; Female; Humans; Male; Radiography
PubMed: 29337631
DOI: 10.2319/111517-787.1 -
Current Osteoporosis Reports Dec 2019This review summarizes recently published data on the effects of pregnancy and lactation on bone structure, mechanical properties, and mechano-responsiveness in an... (Review)
Review
PURPOSE OF REVIEW
This review summarizes recently published data on the effects of pregnancy and lactation on bone structure, mechanical properties, and mechano-responsiveness in an effort to elucidate how the balance between the structural and metabolic functions of the skeleton is achieved during these physiological processes.
RECENT FINDINGS
While pregnancy and lactation induce significant changes in bone density and structure to provide calcium for fetal/infant growth, the maternal physiology also comprises several innate compensatory mechanisms that allow for the maintenance of skeletal mechanical integrity. Both clinical and animal studies suggest that pregnancy and lactation lead to adaptations in cortical bone structure to allow for rapid calcium release from the trabecular compartment while maintaining whole bone stiffness and strength. Moreover, extents of lactation-induced bone loss and weaning-induced recovery are highly dependent on a given bone's load-bearing function, resulting in better protection of the mechanical integrity at critical load-bearing sites. The recent discovery of lactation-induced osteocytic perilacunar/canalicular remodeling (PLR) indicates a new means for osteocytes to modulate mineral homeostasis and tissue-level mechanical properties of the maternal skeleton. Furthermore, lactation-induced PLR may also play an important role in maintaining the maternal skeleton's load-bearing capacity by altering osteocyte's microenvironment and modulating the transmission of anabolic mechanical signals to osteocytes. Both clinical and animal studies show that parity and lactation have no adverse, or a positive effect on bone strength later in life. The skeletal effects during pregnancy and lactation reflect an optimized balance between the mechanical and metabolic functions of the skeleton.
Topics: Adaptation, Physiological; Animals; Biomechanical Phenomena; Bone Density; Bone Remodeling; Bone and Bones; Calcium; Cancellous Bone; Cortical Bone; Female; Humans; Lactation; Osteocytes; Pregnancy; Weaning; Weight-Bearing
PubMed: 31755029
DOI: 10.1007/s11914-019-00555-5 -
The International Journal of... 2021The axial skeleton of the has undergone an evolutionary reduction of its bone elements. This structural plan is strongly preserved throughout the order and would have... (Review)
Review
The axial skeleton of the has undergone an evolutionary reduction of its bone elements. This structural plan is strongly preserved throughout the order and would have emerged as a highly specialized anatomical adaptation to its locomotor jumping pattern. The development programs that direct the vertebral morphogenesis of the anurans are poorly described and the molecular bases that have caused their pattern to differ from other tetrapods are completely unknown. In this work, we review the ontogeny of the spinal column of the anurans and explore the genetic mechanisms that could explain the morphological difference and the maintenance of the body plan during evolution. Here, we propose that the absence of caudal osseous elements, as a consequence of the inability of sclerotomes to form cartilaginous condensations in frogs, could be due to changes in both pattern and expression levels of , , and genes along the anteroposterior axis. The anteriorised expression of the genes together with the reduction in the expression levels of , and in the posterior somites could explain, at least partly, the loss of caudal vertebrae in the anurans during evolution.
Topics: Animals; Anura; Bone and Bones; Gene Expression Regulation, Developmental; Genes, Homeobox; Skeleton; Somites
PubMed: 32930370
DOI: 10.1387/ijdb.200230ss -
Seminars in Cell & Developmental Biology Jul 2019The skull is a vertebrate novelty. Morphological adaptations of the skull are associated with major evolutionary transitions, including the shift to a predatory... (Review)
Review
The skull is a vertebrate novelty. Morphological adaptations of the skull are associated with major evolutionary transitions, including the shift to a predatory lifestyle and the ability to masticate while breathing. These adaptations include the chondrocranium, dermatocranium, articulated jaws, primary and secondary palates, internal choanae, the middle ear, and temporomandibular joint. The incredible adaptive diversity of the vertebrate skull indicates an underlying bauplan that promotes evolvability. Comparative studies in craniofacial development suggest that the craniofacial bauplan includes three secondary organizers, two that are bilaterally placed at the Hinge of the developing jaw, and one situated in the midline of the developing face (the FEZ). These organizers regulate tissue interactions between the cranial neural crest, the neuroepithelium, and facial and pharyngeal epithelia that regulate the development and evolvability of the craniofacial skeleton.
Topics: Animals; Biological Evolution; Body Patterning; Facial Bones; Fishes; Gene Expression Regulation, Developmental; Neural Crest; Skull
PubMed: 29248471
DOI: 10.1016/j.semcdb.2017.12.004 -
Developmental Dynamics : An Official... Apr 2017Here we review studies identifying regulatory networks responsible for synovial, cartilaginous, and fibrous joint development. Synovial joints, characterized by the... (Review)
Review
Here we review studies identifying regulatory networks responsible for synovial, cartilaginous, and fibrous joint development. Synovial joints, characterized by the fluid-filled synovial space between the bones, are found in high-mobility regions and are the most common type of joint. Cartilaginous joints such as the intervertebral disc unite adjacent bones through either a hyaline cartilage or a fibrocartilage intermediate. Fibrous joints, which include the cranial sutures, form a direct union between bones through fibrous connective tissue. We describe how the distinct morphologic and histogenic characteristics of these joint classes are established during embryonic development. Collectively, these studies reveal that despite the heterogeneity of joint strength and mobility, joint development throughout the skeleton utilizes common signaling networks via long-range morphogen gradients and direct cell-cell contact. This suggests that different joint types represent specialized variants of homologous developmental modules. Identifying the unifying aspects of the signaling networks between joint classes allows a more complete understanding of the signaling code for joint formation, which is critical to improving strategies for joint regeneration and repair. Developmental Dynamics 246:262-274, 2017. © 2016 Wiley Periodicals, Inc.
Topics: Animals; Cartilage, Articular; Gene Regulatory Networks; Humans; Joint Capsule; Joints; Morphogenesis; Regeneration; Signal Transduction
PubMed: 27859991
DOI: 10.1002/dvdy.24472