Perlecan/Hspg2 Deficiency Impairs Bone’s Calcium Signaling and Associated Transcriptome in Response to Mechanical Loading

Perlecan,a heparan sulfate proteoglycan,acts as a mechanical sensor for bone to detect external loading.Deficiency of perlecan increases the risk of osteoporosis in patients with Schwartz-Jampel Syndrome(SJS)and attenuates loading4nduced bone formation in perlecan deficient mice(Hypo).Considering that intracellular calcium[Ca2+]i is an ubiquitous messenger controlling numerous cellular processes including mechanotransduction,we hypothesized that perlecan deficiency impairs bone’s calcium signaling in response to loading.To test this,we performed real-time[Ca2+]i imaging on in situ osteocytes of adult murine tibiae under cyclic loading(8 N,Figure 1).Relative to wild type(WT),Hypo osteocytes showed decreases in the overall[Ca2+]i response rate(-58%),calcium peaks(-33%),cells with multiple peaks(-53%),peak magnitude(-6.8%),and recovery speed to baseline(-23%).RNA sequencing and pathway analysis of tibiae from mice subjected to one or seven days of unilateral loading demonstrated that perlecan deficiency significantly suppressed the calcium signaling,ECM-receptor interaction,and focal adhesion pathways following repetitive loading.Defects in the endoplasmic reticulum(ER)calcium cycling regulators such as Ryr1/ryanodine receptors and Atp2a1/Sercal calcium pumps were identified in Hypo bones.Taken together,impaired calcium signaling may contribute to bone’s reduced anabolic response to loading,underlying the osteoporosis risk for the SJS patients.

Paget’s disease of bone: Report of 11 cases

BACKGROUND Paget’s disease of bone(PDB)is a rare metabolic bone disease in China and is characterized by increased bone resorption and disorganized bone formation.The main clinical symptoms of PDB are focal or multiple bone pain and deformity with high disability.The disease has high missed diagnosis and misdiagnosis rates.This report summarizes the clinical manifestations,imaging and pathological features,and treatments of 11 patients with PDB at our hospital from 1993 to 2020 in order to improve the recognition and prognosis of PDB.CASE SUMMARY There were eight male and three female patients whose average age was 48.7±11.0 years with a PDB course of 1-16 years.Nine patients had bone pain and bone deformities in different parts of the body,the majority of which involved the long bones.Laboratory examinations revealed elevated serum alkaline phosphatase(ALP)in all patients with an average of 618±460 IU/L(normal range 0-130 IU/L),and serum calcium and phosphorus levels were in the normal range.Imageology showed that osteolysis was usually combined with osteosclerosis and/or bone deformities in single or multiple bones.^(99m)Tc-methylene diphosphonate bone scintigraphy revealed increased radionuclide uptake in the bone lesions.Six patients underwent bone tissue biopsy,and the typical pathological changes were a mosaic structure of the bone trabeculae with irregularly arranged cement lines and multinuclear osteoclasts.Ten of the 11 patients were effectively treated with bisphosphonates.CONCLUSION Early diagnosis of the rare disease PDB can be made through elevated ALP levels and typical presentations on bone X-ray and from bone tissue biopsy.

Capitate transposition to replace necrotic lunate bone with a pedicle for Kienbock's disease:review of 30 cases

Objective To investigate the clinical application of capitate transposition with a pedicle in 30 cases of Kienbock’s disease.Methods The external diameter and curvature of the capitate head and proximal facet of the lunate were observed and measured in 100 specimens. The vascularity of the capitate was also investigated. Capitate transposition with a vascular pedicle was designed to treat 30 patients with advanced Kienbock’s disease who were followed up for 2 to 16 years and then analyzed according to Evans's scoring system.Results Aseptic necrosis did not occur in the transposed capitate because the pedicle fascia including the dorsal branch of the anterior interosseous artery ensured the vascularity of proximal two thirds of the capitate. The transposed capitate reestablished a relatively pain-free radiocarpal joint. Follow-up results showed that grip strength and motion arc were up to 70% of contralateral side.Conclusions Capitate transposition with a pedicle is a reliable treatment method for advanced Kienbock’s disease,with favorable prognosis for at least five years postoperatively.

Ancient Woman's Bones May Rewrite History

人类学家历来认为,北美洲的最初的居民是由西伯利亚沿今日的白令海峡迁徙到阿拉斯加的。可是,从最近在美国加利福尼亚州西南部的圣罗莎岛上发现的 Ancient Woman’s Bones来看,北美洲的最初的居民似乎是从海上移居而来的玻利尼西亚人或南亚洲人。最新科技测定Woman’s Bones的年龄已经达到13000岁,这又改写了一个历史的结论:…humans arrived in North Americaabout 11,500 years ago。

It’s not just for strong bones and healthy teeth CALCIUM——That "Miracle" Mineral

本文揭示了有关钙的作用的重大新发现。《现代汉语词典》(p.346)标明:钙,金属元素,符号Ca(calcium)。人的血液和骨骼中都含有钙,缺钙会引起佝偻病、手足抽搦等。殊不知,钙竟是 a possible player in the fight against manyailments。诸如:1.抗高血压;2.治心脏病;3.驱妇女经期不适;4.消肾结石;5.医骨质疏松等等。关于第4点,尤为引人深思。For years doctors have told pa-tients who suffer from kidney stones to limit calcium.The reason:calcium is amajor component in about 80 percent of all stones.这个 reason顺理成章。然而,下文叫读者大跌眼镜:But controversial new research suggests that the way toreduce the risk of kidney stones may be to increase calcium intake.此言是否应了汉语“以毒攻毒”之说?1996年7月 11日新民晚报赫然刊登一条新闻:英医学家认为——多吃瘦肉比肥肉更有损健康。因瘦肉在烹煮过程中会产生致癌物质——杂环胺。人类层出不穷的新发现在我们的心底总不得不同时激起一点遗憾的涟漪:我们对周围世界的认识是何等的“初级”,何等的有限。本文详列了各类人的钙的理想摄入量,同时荐介了若干含钙食品。读来亲切。tofu(中国的“豆腐”)也幸列其中。国内食品崇尚洋名?