Re­searchers seek to keep as­tro­nauts from los­ing bone mass by knock­ing genes out of bone-build­ing cells, Honey Tsang re­ports.

China Daily (Hong Kong) - - FOCUS - Contact the writer at hon­eyt­sang@chi­nadai­

On April 20, Tianzhou-1, China’s first cargo space­craft, rock­eted up from Wen­chang Space­craft Launch Site in Hainan prov­ince. It slashed through the dark­ness and headed into space — leav­ing fiery blaze trails and ap­plause.

It was an un­manned space mission but hun­dreds of cul­tured cells — snugly cra­dled aboard the Tianzhou-1 — played a part as stand-in as­tro­nauts in search of a pos­si­ble cure for os­teo­poro­sis.

Os­teoblasts — the tech­ni­cal term for bone-syn­the­siz­ing cells — were the spe­cific cell type packed up and sent into space. For years, sci­en­tists have stud­ied os­teoblas­tic cells on earth for clues about how to hin­der, or at least de­lay, the loss of bone den­sity that comes with age.

In 2012, two medicine ex­perts from Hong Kong — Lyu Aip­ing and Zhang Ge — dis­cov­ered that the CKIP-1 gene, which is ex­pressed in os­teoblasts, is a sig­nif­i­cant in­hibitor of bone for­ma­tion.

The re­searchers con­ducted more ex­per­i­ments, us­ing ad­vanced ge­netic tech­nol­ogy to re­move CKIP1 genes from mouse os­teoblas­tic cells. The re­sult was just as en­cour­ag­ing as ex­pected. Cells with­out CKIP-1 formed much greater and denser bone mass.

The dis­cov­ery has been tried and tested on the ground but Lyu and Zhang at­tempted to make a quan­tum leap. They are mov­ing into an am­bi­tious stage of sci­en­tific ex­plo­ration — can CKIP-1 do the same work in space as it does on earth?

“Study­ing CKIP-1 in space is of con­sid­er­able sci­en­tific im­por­tance,” said Zhang, as­so­ciate di­rec­tor of the Law Sau Fai In­sti­tute for Ad­vanc­ing Trans­la­tional Medicine in Bone and Joint Dis­eases (TMBJ) at Hong Kong Bap­tist Univer­sity (HKBU).

“As hu­mans nor­mally lose 1 to 2 per­cent bone mass in space ev­ery week, know­ing how CKIP-1 func­tions un­der mi­cro­grav­ity might pro­vide po­ten­tial ther­a­peu­tic so­lu­tions to main­tain space crews’ bone health,” he added.

The 1-per­cent loss per week might sound triv­ial, but Zhang stressed it is in fact an alarm­ing amount, “espe­cially when con­sid­er­ing that post­menopausal women lose 1 per­cent bone mass per year in­stead”.

Joint ef­fort in space

The ex­per­i­ment, aimed at re­veal­ing the func­tion­ing of CKIP-1 in os­teoblasts un­der mi­cro­grav­ity, was the only cross-bound­ary space sci­ence project aboard the Tianzhou-1.

The ex­per­i­ment was first pro­posed and led by HKBU’s medicine schol­ars, and over­seen by China Manned Space Engi­neer­ing Of­fice (CMSEO) and Tech­nol­ogy and Engi­neer­ing Cen­ter for Space Uti­liza­tion (CSU) of the Chi­nese Acad­emy of Sciences.

Ever since it was ini­ti­ated in De­cem­ber 2013, the project has pre­oc­cu­pied re­searchers across the bound­ary in years-long prepa­ra­tion.

About a month be­fore Tianzhou-1 lifted off, Hong Kong re­searchers went to Wen­chang launch base and worked metic­u­lously to cul­ture the per­fect batches of mouse os­teoblast cell lines de­voted to the space ex­per­i­ment.

Wang Luyao, an HKBU re­searcher re­spon­si­ble for breed­ing the cell line, said the en­vi­ron­ment in space is starkly dif­fer­ent from that on earth. The team put their noses to the grind­stone to en­gi­neer the cul­tured cells to be ac­cli­ma­tized to cos­mic con­di­tions, she added.

In do­ing so, not only did re­searchers have to re­move CKIP-1 genes from the cell line — which is the very first pre­req­ui­site of the ex­per­i­ment — they also prop­a­gated a new breed of os­teoblas­tic cells that were car­bon diox­ide in­de­pen­dent.

“In gen­eral, car­bon diox­ide is of vi­tal ne­ces­sity for cells to grow bet­ter,” added Wang. “It took us tremen­dous ef­forts to ge­net­i­cally vary the os­teoblasts so that they could sur­vive in space even with­out car­bon diox­ide.”

The os­teoblas­tic cells the Hong Kong re­searchers do­mes­ti­cated stayed in space for about a month. In the course of the ex­per­i­ment, sci­en­tists ex­am­ined the cells via live cell imag­ing sys­tem — a tech­nol­ogy that en­ables sci­en­tists to study cel­lu­lar ac­tiv­i­ties through time-lapse mi­croscopy.

Drift fur­ther

The team’s de­sire to probe the func­tion­ing of CKIP-1 in space is pri­mar­ily driven by a need to safe­guard as­tro­nauts’ bone strength dur­ing lengthy space­flights, which are cen­tral to China’s space ex­pe­di­tion plan.

China’s long­est manned space mission to date was per­formed by Jing Haipeng and Chen Dong, the two as­tro­nauts who spent about a month in space in Oc­to­ber last year.

“The one-month stay was im­pair­ing the bones of the duo,” said Lyu, HKBU’s dean of Chi­nese medicine and di­rec­tor of the TMBJ.

“As they were too weak to walk, they had to be lifted out of the cap­sule with the help of ground per­son­nel once they touched down on earth,” Lyu added.

In fu­ture space mis­sions, China en­vis­ages com­plet­ing the con­struc­tion of an or­bit­ing space sta­tion by about 2022. As­tro­nauts would stay in the space sta­tion for three to six months on ev­ery mission, Yang Li­wei, deputy di­rec­tor of CMSEO, said ear­lier at the 2017 Global Space Ex­plo­ration Con­fer­ence in June in Bei­jing.

Up­com­ing ex­tended space flights cre­ate the press­ing need to stave off bone loss for space crew in a weight­less en­vi­ron­ment, said Liang Chao, an HKBU re­searcher for the ex­per­i­ment, who is also a post­doc­toral re­search fel­low of TMBJ.

Some stud­ies as­serted that a con­stant work-out might help re­store bone strength, but Liang be­lieves “it isn’ t suf­fi­cient to main­tain a good bone health dur­ing month­s­long stint in space.”

This limit has pushed re­searchers ahead to study the CKIP-1 gene in space, hop­ing the gene could fill the void.

Liang told China Daily the re­search team had al­ready fin­ished ex­am­in­ing the time-lapse pho­to­graphs of the cell line through sev­eral con­trol ex­per­i­ments in Ts­inghua Univer­sity in Bei­jing, and they are now de­cod­ing the data. The re­sult is ex­pected to be re­leased in the com­ing months.

If suc­cess­ful, Liang said, the ex­per­i­ment might point to the use of Chi­nese medicine to sup­press the ac­tiv­ity of CKIP-1, as a pre­ven­tive mea­sure against bone loss — which will al­low as­tro­nauts to travel fur­ther in space.

Know­ing how CKIP-1 (gene) func­tions un­der mi­cro­grav­ity might pro­vide po­ten­tial ther­a­peu­tic so­lu­tions to main­tain space crews’ bone health.”

Zhang Ge, as­so­ciate di­rec­tor of the Law Sau Fai In­sti­tute for Ad­vanc­ing Trans­la­tional Medicine in Bone and Joint Dis­eases, Hong Kong Bap­tist Univer­sity

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