Bone marrow adipocytes (BMAds) affect bone homeostasis, but the mechanism remains unclear. Here, we showed that exercise inhibited PCNA clamp-associated factor (PCLAF) secretion from the bone marrow macrophages to inhibit BMAds senescence and thus alleviated skeletal aging. The genetic deletion of PCLAF in macrophages inhibited BMAds senescence and delayed skeletal aging. In contrast, the transplantation of PCLAF-mediated senescent BMAds into the bone marrow of healthy mice suppressed bone turnover. Mechanistically, PCLAF bound to the ADGRL2 receptor to inhibit AKT/mTOR signaling that triggered BMAds senescence and subsequently spread senescence among osteogenic and osteoclastic cells. Of note, we developed a PCLAF-neutralizing antibody and showed its therapeutic effects on skeletal health in old mice. Together, these findings identify PCLAF as an inducer of BMAds senescence and provide a promising way to treat age-related osteoporosis.

UNASSIGNED: Bone tissue engineering (BTE) is a promising alternative to autologous bone grafting for the clinical treatment of bone defects, and inorganic/organic composite hydrogels as BTE scaffolds are a hot spot in current research. The construction of nano-hydroxyapatite/gelatin methacrylate/oxidized sodium alginate (nHAP/GelMA/OSA), abbreviated as HGO, composite hydrogels loaded with bone morphogenetic protein 7 (BMP7) will provide a suitable 3D microenvironment to promote cell aggregation, proliferation, and differentiation, thus facilitating bone repair and regeneration.
UNASSIGNED: Dually-crosslinked hydrogels were fabricated by combining GelMA and OSA, while HGO hydrogels were formulated by incorporating varying amounts of nHAP. The hydrogels were physically and chemically characterized followed by the assessment of their biocompatibility. BMP7-HGO (BHGO) hydrogels were fabricated by incorporating suitable concentrations of BMP7 into HGO hydrogels. The osteogenic potential of BHGO hydrogels was then validated through in vitro experiments and using rat femoral defect models.
UNASSIGNED: The addition of nHAP significantly improved the physical properties of the hydrogel, and the composite hydrogel with 10% nHAP demonstrated the best overall performance among all groups. The selected concentration of HGO hydrogel served as a carrier for BMP7 loading and was evaluated for its osteogenic potential both in vivo and in vitro. The BHGO hydrogel demonstrated superior in vitro osteogenic induction and in vivo potential for repairing bone tissue compared to the outcomes observed in the blank control, BMP7, and HGO groups.
UNASSIGNED: Using hydrogel containing 10% HGO appears promising for bone tissue engineering scaffolds, especially when loaded with BMP7 to boost its osteogenic potential. However, further investigation is needed to optimize the GelMA, OSA, and nHAP ratios, along with the BMP7 concentration, to maximize the osteogenic potential.

Triply periodic minimal surface (TPMS) is widely used because it can be used to control the shape of porous scaffolds precisely by formula. In this paper, an I-wrapped package (I-WP) type porous scaffolds were constructed. The finite element method was used to study the relationship between the wall thickness and period, the morphology and mechanical properties of the scaffolds, as well as to study the compression and fluid properties. It was found that the porosity of I-WP type scaffolds with different wall thicknesses (0.1 ~ 0.2 mm) and periods (I-WP 1 ~ I-WP 5) ranged from 68.01% ~ 96.48%, and the equivalent elastic modulus ranged from 0.655 ~ 18.602 GPa; the stress distribution of the scaffolds tended to be uniform with the increase of periods and wall thicknesses; the equivalent elastic modulus of the I-WP type scaffolds was basically unchanged after the topology optimization, and the permeability was improved by 52.3%. In conclusion, for the I-WP type scaffolds, the period parameter can be adjusted first, then the wall thickness parameter can be controlled. Topology optimization can be combined to meet the design requirements. The I-WP scaffolds constructed in this paper have good mechanical properties and meet the requirements of repairing human bone tissue, which may provide a new choice for the design of artificial bone trabecular scaffolds.
三周期极小曲面（TPMS）可以通过公式精确地控制多孔支架的形态而被广泛应用。本文构建一种I型包装（I-WP）型多孔支架，采用有限元法研究壁厚和周期与支架形态和力学性能的关系，并进行压缩和流体性能的研究。研究发现，不同壁厚（0.1～0.2 mm）、不同周期（I-WP 1～I-WP 5）的I-WP型支架孔隙率在68.01%～96.48%范围内，等效弹性模量为0.655～18.602 GPa；随着周期和壁厚的增加，支架应力分布趋于均匀；拓扑优化后I-WP型支架等效弹性模量基本不变，渗透性提升52.3%。综上，对于I-WP型支架可以先调控周期参数，后调控壁厚参数，结合拓扑优化来达到设计要求。本文构建的I-WP型支架具有良好的力学性能，且满足修复人体骨组织的需求，为人工骨小梁支架的设计提供一种新选择。.

OBJECTIVE: To investigate the clinical significance of bone metabolic indexes for disease assessment and curative effect monitoring in multiple myeloma (MM) bone disease (MBD) patients with different blood separation results.
METHODS: A total of 134 newly diagnosed MM patients treated in Cangzhou Hospital of Integrated TCM-WM-Hebei were enrolled and divided into control group [119 cases, serum, colloid and red blood cell (RBC) from top to bottom of sample] and abnormal group (15 cases, serum, mixed layer of RBC and serum, colloid and RBC from top to bottom of sample) according to the results of blood separation. According to the imaging findings, MBD was classified into grade 0-4, grade 0-2 was mild, and grade 3-4 was severe. The MBD grade of patients in the two groups was analyzed. The curative effect of MBD patients after chemotherapy and the changes of blood separation results and bone metabolic indexes before and after treatment were evaluated. The correlation between β2-microglobulin (MG) and bone metabolic indexes was analyzed by Pearson correlation analysis.
RESULTS: In the control group, there were 69 cases of grade 0-2 and 50 cases of grade 3-4, while in the abnormal group, there were 5 cases of grade 0-2 and 10 cases of grade 3-4, the difference was statistically significant (P < 0.05). The serum β2-MG, β-CTX levels in abnormal group were both significantly higher than those in control group, while the levels of P1NP and osteocalcin (OC) were significantly lower (all P < 0.001). In the control group, there were 95 patients with ≥ partial response (PR) and the blood separation results were not changed, while 24 patients with 0.05). Compared with before treatment, the levels of β-CTX and β2-MG in the control group with unchanged blood separation results were significantly decreased (both P < 0.001), while the levels of P1NP and OC were significantly increased (P < 0.01, P < 0.001), and the level of each index in the patients transformed to abnormal blood separation result after treatment did not significantly change (P >0.05); the levels of β-CTX and β2-MG in the abnormal group transformed to normal blood separation result were significantly decreased (both P < 0.01), while the levels of P1NP and OC were significantly increased (P < 0.001, P < 0.01), and the level of each index in patients with unchanged blood separation results did not significantly change (P>0.05). Pearson correlation analysis showed that serum β2-MG was positively correlated with β-CTX (r =0.709, P < 0.001), and negatively correlated with P1NP and OC (r =-0.410,r =-0.412, both P < 0.001).
CONCLUSIONS: MBD patients with abnormal blood separation results have higher bone disease grade and poor prognosis, which is closely related to the significant increase of bone resorption index β-CTX level and decrease of bone formation index P1NP and OC levels, leading to more serious bone metabolic homeostasis disorder. The results of blood separation combined with the changes of bone metabolic indexes can be used as one of the comprehensive predictors of disease condition, efficacy monitoring and prognosis evaluation of MBD patients.
UNASSIGNED: 不同血液分离结果的多发性骨髓瘤骨病患者骨代谢水平研究.
UNASSIGNED: 探讨不同血液分离结果的骨髓瘤骨病（MBD）患者骨代谢指标对病情评估及疗效监测的临床意义。.
UNASSIGNED: 纳入2016年3月至2020年3月河北省沧州中西医结合医院收治的134例初诊MM患者，根据血液离心结果，分为对照组119例（样本自上而下依次为血清、胶体、红细胞），异常组15例（样本自上而下依次为血清、红细胞、胶体、红细胞），根据影像学表现将MBD分为0-4级，0-2级为骨病较轻者，3-4级为骨病较重者，分析两组患者MBD的分级情况，并对不同血液分离结果的MBD患者进行疗效评价，分析治疗前后血液分离结果及骨代谢指标水平的变化，采用Pearson相关分析法分析β2-微球蛋白（MG）与骨代谢指标水平的相关性。.
UNASSIGNED: 对照组0-2级69例，3-4级50例；异常组0-2级5例，3-4级10例，比较差异具有统计学意义（P < 0.05）。异常组血清β2-MG、Ⅰ型胶原羧基端肽β特殊序列（β-CTX）水平显著高于对照组，而Ⅰ型前胶原氨基端前肽（P1NP）、骨钙素（OC）水平显著低于对照组（均P < 0.001）。对照组95例疗效≥部分缓解（PR），其血液分离结果未改变；24例疗效< PR，其中5例血液分离结果转为异常。异常组9例疗效≥PR，血液分离结果均转为正常；6例疗效< PR，其中5例血液分离结果仍为异常。与治疗前相比，对照组疗效≥PR的患者β-CTX、β2-MG水平显著降低，而P1NP、OC水平显著升高（均P < 0.001）；异常组疗效≥PR的患者β-CTX、β2-MG水平亦显著降低（P < 0.001，P < 0.01），而P1NP、OC水平显著升高（P < 0.001，P < 0.01）。两组疗效 < PR的患者各指标水平与治疗前相比无明显变化（P >0.05）。与疗前相比，对照组治疗后血液分离结果未改变的患者β-CTX、β2-MG水平显著降低（均P < 0.001），P1NP、OC水平显著升高（P < 0.01，P < 0.001），而血液分离结果转为异常的患者各指标水平无明显变化（P >0.05）；异常组治疗后血液分离结果转为正常的患者β-CTX、β2-MG水平显著降低（均P < 0.01），P1NP、OC水平显著升高（P < 0.001，P < 0.01），而血液分离结果未改变的患者各指标水平无明显变化。Pearson相关分析显示，患者血清β2-MG与β-CTX水平呈正相关（r =0.709，P < 0.001），与P1NP、OC水平呈负相关（r =-0.410、-0.412，均P < 0.001）。.
UNASSIGNED: 存在血液异常分离结果的MBD患者骨病分级较高、预后较差，与骨吸收指标β-CTX水平显著升高，骨形成指标P1NP、OC水平显著降低，引起更严重的骨代谢动态平衡紊乱密切相关。血液分离结果联合骨代谢指标水平的变化可作为MBD患者病情、疗效监测及预后评估的综合预测指标之一。.

BACKGROUND: Menkes disease (MD) is a rare, inherited, multisystemic copper metabolism disorder. Classical Menkes disease is characterized by low serum copper and ceruloplasmin concentrations, leading to multiple abnormalities in the whole-body, especially in connective tissue and central nervous system. However, serum copper and ceruloplasmin levels are not reliable diagnostic biomarkers due to the low concentrations in healthy newborns either. The featured imaging manifestations play an important role in diagnosing Menkes disease. To our knowledge, there are few reports on the systemic imaging manifestations of Menkes disease.
METHODS: A 4-month-old male patient presented with recurrent seizures. He had cognitive, intellectual, growth, gross motor, precision movement, and language developmental lags. The patient\'s hemoglobin and serum ceruloplasmin level were low. On MRI, increased intracranial vascular tortuosity, cerebral and cerebellar atrophy, white matter changes, and basal ganglia abnormalities were observed. Plain radiograph revealed wormian bones, rib flaring, metaphyseal spurring, and periosteal reactions in the long bones of the limbs. A pathogenic variant in ATP7A gene was identified in the patient, so he was confirmed the diagnosis of Menkes disease. His symptoms did not improve despite symptomatic and supportive treatment during his hospitalization. Unfortunately, the infant died 3 months after leaving hospital.
CONCLUSIONS: A comprehensive and intuitive understanding of the disease\'s imaging manifestations can help clinicians to identify the disease and avoid delays in care.

Physiological processes within the human body are regulated in approximately 24-h cycles known as circadian rhythms, serving to adapt to environmental changes. Bone rhythms play pivotal roles in bone development, metabolism, mineralization, and remodeling processes. Bone rhythms exhibit cell specificity, and different cells in bone display various expressions of clock genes. Multiple environmental factors, including light, feeding, exercise, and temperature, affect bone diurnal rhythms through the sympathetic nervous system and various hormones. Disruptions in bone diurnal rhythms contribute to the onset of skeletal disorders such as osteoporosis, osteoarthritis and skeletal hypoplasia. Conversely, these bone diseases can be effectively treated when aimed at the circadian clock in bone cells, including the rhythmic expressions of clock genes and drug targets. In this review, we describe the unique circadian rhythms in physiological activities of various bone cells. Then we summarize the factors synchronizing the diurnal rhythms of bone with the underlying mechanisms. Based on the review, we aim to build an overall understanding of the diurnal rhythms in bone and summarize the new preventive and therapeutic strategies for bone disorders.

This study introduces a multi-parameter design methodology to create triply periodic minimal surface (TPMS) scaffolds with predefined geometric characteristics. The level-set constant and unit cell lengths are systematically correlated with targeted porosity and minimum pore sizes. Network and sheet scaffolds featuring diamond, gyroid, and primitive level-set structures are generated. Three radially graded schemes are applied to each of the six scaffold type, accommodating radial variations in porosity and pore sizes. Computer simulations are conducted to assess the biomechanical performance of 18 scaffold models. Results disclose that diamond and gyroid scaffolds exhibit more expansive design ranges than primitive counterparts. While primitive scaffolds display the highest Young\'s modulus and permeability, their lower yield strength and mesenchymal stem cell (MSC) adhesion render them unsuitable for bone scaffolds. Gyroid scaffolds demonstrate superior mechanical and permeability performances, albeit with slightly lower MSC adhesion than diamond scaffolds. Sheet scaffolds, characterized by more uniform material distribution, exhibit superior mechanical performance in various directions, despite slightly lower permeability. The higher specific surface area of sheet scaffolds contributes to elevated MSC adhesion. The stimulus factor analysis also revealed the superior differentiation potential of sheet scaffolds over network ones. The diamond sheet type demonstrated the optimal differentiation. Introducing radial gradations enhances axial mechanical performance at the expense of radial mechanical performance. Radially decreasing porosity displays the highest permeability, MSC adhesion, and differentiation capability, aligning with the structural characteristics of human bones. This study underscores the crucial need to balance diverse biomechanical properties of TPMS scaffolds for bone tissue engineering.

Recently, environmental temperature has been shown to regulate bone homeostasis. However, the mechanisms by which cold exposure affects bone mass remain unclear. In our present study, we observed that exposure to cold temperature (CT) decreased bone mass and quality in mice. Furthermore, a transplant of exosomes derived from the plasma of mice exposed to cold temperature (CT-EXO) can also impair the osteogenic differentiation of BMSCs and decrease bone mass by inhibiting autophagic activity. Rapamycin, a potent inducer of autophagy, can reverse cold exposure or CT-EXO-induced bone loss. Microarray sequencing revealed that cold exposure increases the miR-25-3p level in CT-EXO. Mechanistic studies showed that miR-25-3p can inhibit the osteogenic differentiation and autophagic activity of BMSCs. It is shown that inhibition of exosomes release or downregulation of miR-25-3p level can suppress CT-induced bone loss. This study identifies that CT-EXO mediates CT-induced osteoporotic effects through miR-25-3p by inhibiting autophagy via targeting SATB2, presenting a novel mechanism underlying the effect of cold temperature on bone mass.

Aging is an inevitable physiological process, often accompanied by age-related bone loss and subsequent bone-related diseases that pose serious health risks. Research on skeletal diseases caused by aging in humans is challenging due to lengthy study durations, difficulties in sampling, regional variability, and substantial investment. Consequently, mice are preferred for such studies due to their similar motor system structure and function to humans, ease of handling and care, low cost, and short generation time. In this review, we present a comprehensive overview of the characteristics, limitations, applicability, bone phenotypes, and treatment methods in naturally aging mice and prematurely aging mouse models (including SAMP6, POLG mutant, LMNA, SIRT6, ZMPSTE24, TFAM, ERCC1, WERNER, and KL/KL-deficient mice). We also summarize the molecular mechanisms of these aging mouse models, including cellular DNA damage response, senescence-related secretory phenotype, telomere shortening, oxidative stress, bone marrow mesenchymal stem cell (BMSC) abnormalities, and mitochondrial dysfunction. Overall, this review aims to enhance our understanding of the pathogenesis of aging-related bone diseases.
衰老是一个不可避免的生理过程。随着年龄的增长，骨骼常伴随着年龄相关性的骨质流失，进而发生一系列严重威胁人体健康的骨相关疾病。如果以人作为研究对象进行衰老引起的骨骼疾病的研究，将面临着研究时间长、采样不方便、受区域因素影响较大、投入大等问题。小鼠运动系统的结构和功能与人类相似，控制简单，易于获取，成本低，生成时间短，是相对其他实验动物更适合研究衰老对骨骼系统影响的研究对象。因此，该文就自然衰老小鼠和早衰小鼠 (包括 SAMP6小鼠、POLG小鼠、 LMNA小鼠、 SIRT6小鼠、 ZMPSTE24小鼠、 TFAM小鼠、 ERCC1小鼠、 WERNER小鼠和 KL/KL缺陷小鼠)的特点、局限性、应用范围、骨表型及治疗方法进行综述。另外，该文也对上述衰老小鼠模型的作用机制进行了总结，包括细胞DNA损伤反应、衰老相关分泌表型、端粒缩短、氧化应激、骨髓干细胞异常和线粒体功能障碍。希望本文的综述能对了解衰老相关骨病的发病机制有所帮助。.

Skin problems caused by aging have attracted much attention, and marine collagen peptides have been proved to improve these problems, while mammalian collagen peptides are rarely reported. In this study, fermented deer bone collagen peptide (FCP) and non-fermented deer bone collagen peptide (NCP) were extracted from fermented and non-fermented deer bone, respectively, and their peptide sequences and differential proteins were analyzed using LC-MS/MS technology. After they were applied to aging mice induced with D-gal, the skin hydration ability, antioxidant ability, collagen synthesis, and degradation ability of the mice were studied. The results show that FCP and NCP are mainly peptides that constitute type Ⅰ collagen, and their peptide segments are different. In vivo experiments show that FCP and NCP can improve the richness of collagen fibers in the skin of aging mice; improve the hydration ability of skin; promote the activity of antioxidant-related enzymes; and also show that through the TGF-β and MAPK pathways, the synthesis and degradation of collagen in skin are regulated. These results show that deer bone collagen peptide can improve skin problems caused by aging, promote skin hydration and antioxidant capacity of aging mice, and regulate collagen synthesis and degradation through the MAPK pathway.