生物谷報道：賓夕法尼亞州大學醫(yī)學院的研究人員通過研究某個基因的功能,，發(fā)現(xiàn)抑制骨衰老和刺激骨形成是可以同時發(fā)生的,。這一觀點可用于骨質(zhì)疏松和其他骨疾病的治療。該研究發(fā)表于Nature Medicine.雜志12月刊,，由Yongwon Choi博士（賓夕法尼亞州大學病理和醫(yī)學實驗室教授）和他的同事共同完成。
   在美國,，數(shù)以百萬計的老年人患有骨質(zhì)疏松,，嚴重影響了他們的生活質(zhì)量。隨著人口的老齡化,，骨質(zhì)疏松將成為更大的問題,。骨質(zhì)疏松的治療現(xiàn)在面臨的主要挑戰(zhàn)是，如何阻止骨衰老同時又促進骨生成,。.目前,，骨代謝的機制還不甚清楚，因此用于骨質(zhì)疏松治療的藥物還不多,。破骨細胞可引起骨衰老,，大多數(shù)治療骨質(zhì)疏松的藥物都是通過抑制破骨細胞而起作用的。但是，至少有一種藥物是通過刺激成骨細胞而起作用,，成骨細胞可促進骨形成,。聯(lián)合治療不僅可以預防骨質(zhì)疏松，而且可以改善骨質(zhì)量,。
    賓夕法尼亞州大學醫(yī)學院的發(fā)現(xiàn)證明,，抑制破骨細胞又同時促進新骨形成是可以實現(xiàn)的。骨骼健康是由破骨細胞和成骨細胞之間的動態(tài)平衡維系的,。研究表明,，小鼠Atp6v0d2基因的失活，導致骨量顯著增加,，其主要原因為破骨細胞功能缺失和骨形成增加,。這些結(jié)果闡明了一些骨代謝的機制，并表明通過作用單個基因就可以既抑制骨衰老又同時促進骨形成,。研究人員將對這個基因的上下游基因進行研究,。如果能夠找到作用于靶基因的藥物，就可以幫助數(shù)百萬的骨質(zhì)疏松老年患者,。

Figure 1. Deletion of Atp6v0d2 leads to defective osteoclasts and increased bone formation.

(a) Top, confirmation of Atp6v0d2 deletion by Southern blot. Genomic DNA from Atp6v0d2+/+(wild-type, WT), Atp6v0d2+/- and Atp6v0d2-/- mice was isolated, digested with SphI, and probed with "Probe 1" (see Supplementary Fig. 1). Wild-type and null alleles were 5 kb and 3.7 kb, respectively, in length. Middle, Atp6v0d2 RNA expression in osteoclasts. Bottom, Atp6v0d2 protein expression. Whole-cell extracts from wild-type osteoclast precursors (BMM) and from wild-type or Atp6v0d2-/- osteoclasts were examined with rabbit Atp6v0d2-specific polyclonal antibody by western blot analysis. (b) Tibias, femurs and vertebra from 8- to 10-week-old control, wild-type and Atp6v0d2-/- mice were examined by CT. Two-dimensional (left) and three-dimensional (right) reconstruction of femurs revealed increased bone mass in Atp6v0d2-/- mice compared with control littermates. Histograms represent three-dimensional trabecular structural parameters in the secondary spongiosa of the distal femur: bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular spacing (Tb.Sp) and trabecular connectivity density (Conn-Dens). * P < 0.05. Data represent mean s.e.m. n = 6–8. (c) Static histomorphometry analysis of femurs from 6- to 7-week-old Atp6v0d2-/- mice and control littermates: bone volume (BV/TV), osteoclast surface per bone surface (OcS/BS), osteoblast surface per bone surface (ObS/BS) and osteoclast number per bone surface (NOc/BS). * P < 0.005, † P < 0.05. Data represent mean s.e.m. n = 4. (d) Serum TRACP5b levels were measured by ELISA. (e) Alcian blue staining on femurs from 6- to 7-week-old Atp6v0d2-/- mice and control littermates. (f) Serum type 1 collagen cross-linked telopeptide (CTX) measured by ELISA. * P < 0.05. (g) Dynamic histomorphometry analysis of femurs from 6- to 7-week-old Atp6v0d2-/- mice and control littermates: mineral apposition rate (MAR), bone formation rate (trabecular bone surface) (BFR/BS) and mineralizing surface (MS/BS). * P < 0.05, † P < 0.01. Data represent mean s.e.m. n = 4–5. Scale bar, 100 m. For values other than those presented here, see Supplementary Table 1. NS, not significant.
 
原文出處：
Nature Medcine  December 2006, Volume 12 No 12
Published online: 26 November 2006; | doi:10.1038/nm1514
v-ATPase V0 subunit d2–deficient mice exhibit impaired osteoclast fusion and increased bone formation pp1403 - 1409
Seoung-Hoon Lee, Jaerang Rho, Daewon Jeong, Jai-Yoon Sul, Taesoo Kim, Nacksung Kim, Ju-Seob Kang, Takeshi Miyamoto, Toshio Suda, Sun-Kyeong Lee, Robert J Pignolo, Boguslawa Koczon-Jaremko, Joseph Lorenzo & Yongwon Choi
Published online: 26 November 2006 | doi:10.1038/nm1514
Abstract | Full text | PDF (641K)  | Supplementary Information
See also: News and Views by Boyce & Xing
 
 
相關基因：
Atp6v0d2
Official Symbol: Atp6v0d2 and Name: ATPase, H+ transporting, lysosomal V0 subunit D2 [Mus musculus]
Other Aliases: 1620401A02Rik, AI324824, V-ATPase
Other Designations: ATPase, H+ transporting, V0 subunit D isoform 2; ATPase, H+ transporting, V0 subunit D, isoform 2; vacuolar proton-translocating ATPase d subunit d2
Chromosome: 4; Location: 4 A3
GeneID: 242341
ATP6V0D2
Official Symbol: ATP6V0D2 and Name: ATPase, H+ transporting, lysosomal 38kDa, V0 subunit d2 [Homo sapiens]
Other Aliases: ATP6D2, FLJ38708, VMA6
Other Designations: ATPase, H+ transporting, lysosomal 38kD, V0 subunit d isoform 2; ATPase, H+ transporting, lysosomal 38kDa, V0 subunit D2
Chromosome: 8
GeneID: 245972
 
 
作者簡介：
Dr. Yongwon Choi, Ph.D.
Professor, Department of Pathology and Laboratory Medicine
Investigator, Abramson Family Cancer Research Institute
University of Pennsylvania School of Medicine
Room 308, BRB II/III
421 Curie Blvd.
Philadelphia, PA 19104
Research interests: http://www.uphs.upenn.edu/abramson/choi.html
最近,， Choi博士，由于其在骨免疫學方面所做的貢獻,，獲得了韓國著名的Ho-Am獎提名,。Ho-Am獎授予那些做出杰出成就（促進學科長足發(fā)展并具有國際一流水準的成就）以及成為學術界楷模的學者和研究人員。Choi來自韓國漢城,，2001年以來就職于賓夕法尼亞大學,。