Relations between Meckel's cartilage and the morphogenesis of the mandible in the human embryo

Summary Based on a series of human embryos classified in stages [28], the authors studied the evolution of Meckel's cartilage in its ventral portion and its relations to the morphogenesis of the mandible. Three stages appeared particularly important: stage 16, appearance of Meckel's cartilage; stage 20, beginning of membranous ossification; and stage 23, end of the embryonic period (8th week). The primitive bony nodule which develops from the embryonic mesenchyme appears as a double bony layer forming a groove containing the neurovascular bundle, into which the dental lamina is also invaginated.

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Relations entre le cartilage de Meckel et la morphogénèse de la mandibule chez l'embryon humain

Résumé A partir d'une série d'embryons humains classés en stades [28], les auteurs étudient l'évolution du cartilage de Meckel dans sa portion ventrale et ses relations avec la morphogénèse de la mandibule. Trois stades apparaissent comme particulièrement importants : Stade 16 : Apparition du cartilage de Meckel ; Stade 20 : Début de l'ossification membraneuse. Stade 23 : Fin de la période embryonnaire (8ème semaine). Le nodule osseux primitif, qui s'est formé aux dépens du mésenchyme embryonnaire, se présente sous l'aspect d'une double lame osseuse formant une gouttière, lit du paquet vasculo-nerveux, dans laquelle vient également s'invaginer la lame dentaire.

     

The effects of high dose of parathyroid hormone on fetal osteoclasts and their precursors in vivo: An ultrastructural-cytochemical study

Background: It is not well known how the immediate precursors of osteoclast develop into osteoclasts in the fetus. This ultrastructural-cytochemical study was designed to clarify the formation process of the osteoclasts and their increased activities in the fetal mouse limb buds after administration of high dose parathyroid hormone (PTH). Methods: Twenty-four or forty-eight hours after the high doses of PTH were injected into amniotic fluid of the pregnant C₃H mice, the femoral limb buds of embryos were dissected out. Tartrate-resistant acid phosphatase (TRAP) reactions were performed while preparing specimens for electron microscopy. Results: Both control and PTH-given preosteoclasts and osteoclasts exhibited TRAP-positivities in dense bodies and vesicles. As effects of PTH, a binucleated preosteoclast of tandem fashion was observed. More osteoclastic hyperactivities were observed in the diaphyseal bone marrow. An osteoclast with a large cytoplasm exhibited two sets of clear zones and ruffled borders. Some osteoclasts demonstrated prominent amoeboid figures, while other osteoclasts developed large cytoplasmic vacuoles, which contained pieces of calcified chondroid bars. Conclusions: Our results revealed the progression of maturation from young preosteoclasts to osteoclasts. An existence of a peculiar binucleated preosteoclasts suggested one of the processes for multinucleation of the osteoclast. Quite remarkable osteoclastic hyperactivities were obviously the effects of high dose PTH. Our results also indicated the endophagocytic ability of the osteoclast. How PTH affected the osteoclasts and their precursors in the diaphyseal bone marrow can be speculated. © 1995 Wiley-Liss, Inc.     

Heterotopic Ossification Negatively Influences Range of Motion After Revision Total Knee Arthroplasty

BackgroundThe incidence of heterotopic ossification (HO) after total knee arthroplasty (TKA) varies and is of unclear clinical significance. This study aimed to identify the incidence of HO in patients undergoing revision TKA for either stiffness or aseptic loosening/instability and determine if the presence of HO is associated with inferior absolute range of motion (ROM) and ROM gains.MethodsEighty-seven patients were prospectively enrolled and separated into 2 cohorts to evaluate ROM after revision TKA (2017-2019). Group 1 (N = 40) patients were revised for stiffness, while group 2 (N = 47) patients were revised for either aseptic loosening or instability. Goniometer-measured ROM values were obtained preoperatively and at 6 weeks, 6 months, and 1 year postoperatively. Statistical analysis included a Fisher’s exact test to assess for an association between preoperative HO and final ROM at 1 year after revision TKA.ResultsHO was identified on preoperative radiographs in 17 patients (20%). There was a significantly higher rate of preoperative HO in patients revised for stiffness compared to patients revised for instability or loosening (30% vs 11%; P = .03). Five cases of HO qualitatively identified as most clinically severe were associated with lower ROM at each time point compared to the remainder of HO cases in this study cohort (P < .02).ConclusionThe presence of HO is greater in patients undergoing revision TKA for stiffness. Additionally, HO severity appears to have a major effect on preoperative and postoperative ROM trajectory. This information should help guide patient expectations and highlight the need for a comprehensive, standardized classification system for HO.     

GNAS gene mutations affecting XLαs and bone health: A long neglected relationship

The GNAS locus is an imprinted site. The α-subunit of the stimulatory G protein (Gsα) and extralarge variant (XLαs) are the two important products of the GNAS locus. The abnormal expression of Gsα is associated with pseudohypoparathyroidism (PHP) and related disorders, including Albright hereditary osteodystrophy (AHO), pseudopseudohypoparathyroidism (PPHP), and progressive osseous heteroplasia (POH). XLαs protein can mimic the catalytic intracellular synthesis of cyclic adenosine monophosphate (cAMP) by Gsα in response to parathyroid hormone (PTH) stimulation, which may be involved in the pathogenesis of PPHP and POH in patients with paternal GNAS defects. A paternally inherited nonsense variant in the first exon of XLαs in an adult patient may be associated with fractures and osteopetrosis. The relationship between the XLαs product of the GNAS locus and bone remodeling may have been overlooked. Here, we summarize the phenotypes of genetic mouse models and clinical cases of XLαs variations and suggest that the abnormal paternal expression of XLαs may be associated with the development of POH and affect osteoblast and osteoclast differentiation.     

Ossification and pseudoepiphysis formation in the “nonepiphyseal” end of bones of the hands and feet

Metacarpals, metatarsals, and phalanges were studied to assess the developmental morphology of secondary ossification in the nonepiphyseal ends of these bones as well as the formation of the pseudoepiphysis as an epiphyseal ossification variant. Both direct ossification extension from the metaphysis into the epiphysis and pseudoepiphysis formation preceded, and continued to be more mature than, formation and expansion of the classic epiphyseal (secondary) ossification center at the opposite end of each specific bone. Direct metaphyseal to epiphyseal ossification usually started centrally and expanded hemispherically, replacing both physeal and epiphyseal cartilage simultaneously. In contrast, when remnants of physis were retained, while juxtaposed epiphyseal cartilage was replaced, a pseudoepiphysis formed. There were three basic patterns of pseudoepiphysis formation. First, a central osseous bridge extended from the metaphysis across the physis into the epiphysis and subsequently expanded to create a mushroom-like osseous structure. In the second pattern a peripheral osseous bridge formed, creating either an osseous ring or an eccentric bridge between the metaphysis and the epiphysis. In the third pattern, multiple bridging occurred. In each situation the associated remnant physis lacked typical cell columns and was incapable of significantly contributing to the postnatal longitudinal growth of the involved bone. Pseudoepiphyses were well formed by 4–5 years and coalesced with the rest of the bone months of years before skeletal maturation was attained at the opposite epiphyseal end, which ossified in the typical pattern (i.e., formation of a secondary center de novo completely within the cartilaginous epiphysis). This process may also affect the development and appearance of ossification within the longitudinal epiphyseal bracket (delta phalanx).     

黄韧带骨化的病理组织学研究

目的 :探讨黄韧带骨化的病理变化特点和发生机理。方法 :利用组织病理学和组织化学方法对比研究正常黄韧带和 5例病变黄韧带的病理形态学特点、胶原纤维、网状纤维、弹力纤维以及粘液物质的改变。结果 :根据大体形态特点可将黄韧带骨化分为结节型 (增生性 )骨化、周围型骨化和弥漫型骨化 3种类型。组织学上可见病变早期出现胶原纤维肿胀、融合 ,进一步发生软骨化生 ,最终出现钙化和骨化。在肿胀融合的胶原纤维和软骨化生处可见阿新蓝 (pH 2 5 )阳性的粘液性物质。结论 :黄韧带骨化的大体类型代表着同一病变发展的不同阶段 ;韧带的退行性改变是黄韧带骨化的基本原因 ;胶原纤维的肿胀融合及其粘液样变性是黄韧带骨化的起始病变。     

Kinetics of β-glycerophosphate-induced endochondral mineralization In vitro. Calcium accumulation,alkaline phosphatase activity,and effects of levamisole

Summary Isolated mesenchymal limb bud cells from day-12 mouse embryos grown at high density in organoid culture at the medium/air interphase differentiate into chondrocytes and form cartilage nodules. Upon addition of -glycerophosphate (-GP), cartilage undergoes endochondral mineralization. This -GP-induced mineralization was investigated by measuring the calcium content in the cultures and the activity of alkaline phosphatase (AP) in the cell mass and the medium. Calcium incorporation depended on the amount of -GP added. After continuous treatment, mineralization began on day 8 of the culture period and increased linearly until day 15. In long-term cultures, periodical treatment for 6 days caused an increase in mineralization the older the cultures were, but the slope of increase was proportionately less steep. Treatment at the latest period on days 19–24 resulted in a markedly reduced mineralization. After short-term treatment (48 hours), mineralization increased also the older the cultures were and proceeded during further cultivation in -GP-free medium. This kinetic behavior indicates a dependency of mineralization on cartilage maturation in this in vitro system. AP activity increased enormously and nearly logarithmically in the cell mass in -GP-free medium, whereas -GP treatment inhibited this drastic increase. In the medium, considerable activities of AP were also measurable from day 10 onward. It increased in -GP-free medium up to day 14, but was diminished after mineralization had been induced. Levamisole inhibited AP activity dose dependently when added directly to the enzyme-containing medium (100% inhibition at 10^-3 M). Added to the cultures from day 7 to 14, it partially inhibited AP activity and mineralization at 5×10^-5 M; mineralization was totally inhibited at 10^-3 M, but AP activity was still present. This high concentration was cytotoxic, as revealed ultrastructurally and by GAG estimation. This in vitro system comprises cartilage development and maturation, -GP-inducible endochondral mineralization, and final degenerative changes; it may be an appropriate model for investigations on endochondral mineralization.     

双侧耳郭软骨骨化1例并文献复习

目的 探讨耳郭软骨骨化的发病机制、临床表现、诊断依据、鉴别诊断、治疗方法。方法 回顾性分析1例耳郭软骨骨化患者的临床资料并复习相关文献进行总结。结果 耳郭软骨骨化的发病机制暂不明确,通常无明显不适症状,少数患者可伴有局部疼痛、听力下降等症状。颞骨CT可辅助诊断,最终确诊依赖于组织病理检查。症状不明显时可暂予观察,若症状严重影响了生活和工作,可予手术治疗。结论 耳郭软骨骨化在临床上较为少见,目前尚无有效逆转耳郭骨化的办法。积极寻找病因,及早干预,有利于避免病情进一步发展。