Te kahurangi metilīni me te koroheketanga o te kōiwi: he aha i kore ai ngā kitenga pūtau e matapae i ngā hua mō ngā wheua kiore

Whakaarohia tētahi pūhui e whakatau ana i ngā pūtau tonu e kai ana i te wheua, kua whakamātauria ki tētahi rīhi, ā, e mahi ana kia rite tonu ki ngā tūmanako. He iti ake ngā pūtau wāwāhi wheua, arā, ngā osteoclast, he maha ō rātou karihi; he mārama te urupare ki te horopeta; he whakamārama whaitake hoki e pā ana ki ngā mitokōria. Kātahi ka hoatu taua pūhui ki ngā kiore mō te nuinga o tō rātou oranga pakeke, ka matawaingia ō rātou kōiwi ki ngā ahu e toru, ā, kāore he rerekētanga. He āhua tawhito tonu ngā wheua tawhito, ahakoa i hoatu te pūhui, kāore rānei.

Koia te whakaaturanga pono o tētahi rangahau i te tau 2024. He take nui kia mārama pū ki taua rangahau, nā te mea kei te wāhi tonu ia e ngoikore ai te nuinga o ngā kerēme mō ngā tāpiringa me ngā wheua. Nā Poudel me ōna hoa te pepa, i whakaputaina ki Aging i te Maehe 2024, ā, e wātea ana ki te katoa, nō reira ka taea te whakataurite i ia inenga kei raro nei ki te pūtake. Ko tōna hua matua, kāore i kitea he pānga. Ehara te kore kitea o tētahi pānga i te rahunga. He whakautu kē, ā, he pai te whakautu a tēnei rangahau i tētahi pātai whāiti: ka tiakina rānei te kōiwi kiore e koroheketia ana e te hoatutanga pūhui ārai hāoratanga ki te tinana katoa mō te wā roa, arā, te kahurangi metilīni, te mitokinōne rānei? Kāo.

Te āhua o te koroheketanga wheua i ngā tau inenga

Ehara te ngaronga wheua nā te pakeketanga i te āhuatanga kotahi, nō reira kāore te rangahau i ine i te mea kotahi anake. Mā te matawai rorohiko moroiti, i matawai ngā kairangahau i ngā wāhi kōiwi e toru: te wheua mārō o waho i te wāhanga waenganui o te kakau o te wheua kūhā, te wheua kōputaputa i te metaphysis o te pito raro o te wheua kūhā, arā, te kupenga āhua hautai e tata ana ki te hononga, me te wheua kōputaputa i te ira tuarā tuarima o te hope. I ia wāhi, i tuhia ngā tawhā paerewa mō te hanganga moroiti. Ko te BV/TV te hautanga o tētahi rōrahi he wheua, kaua ko te wāhi mō te hinu wheua. Ko te BMD te kiato kohuke. E whakaahua ana te Tb.Th, te Tb.N me te Tb.Sp i te mātotoru, te maha me te tawhiti i waenga i ngā kurupae wheua moroiti. E whakaahua ana te mātotoru o te wheua mārō o waho me ngā horahanga tapahanga whakawhiti i te kakau.

Whakaarohia te wheua kōputaputa hei anga tautoko i roto i tētahi whare putunga. Ka tangohia katoatia ētahi pou e te koroheketanga, ka whakakikokoretia hoki ērā atu. Nā reira, ka heke te hautanga o te wāhi e kīia ana e te hanganga, ka nui ake te tawhiti i waenga i ngā pou e toe ana, ā, ka iti ake te taumaha e taea ana e te anga katoa te kawe. Ko te wheua mārō o waho te pakitara tonu o te whare putunga, e kikokore haere ana. Me kitea te pānga o tētahi maimoatanga e tiaki ana i te kōiwi i ēnei tau inenga. Koia te whakamātautau i whakamahia e te rangahau.

Ngā mea i puta i te rīhi

I whakamahia e ngā whakamātautau pūtau te hinu wheua i tangohia mai i ngā wheua kūhā me ngā wheua tāhau o ngā kiore UM-HET3 e 6 ki te 7 marama te pakeke. He momo kiore kanorau ā-ira tēnei, i whakatipuria mō te rangahau koroheketanga. E whā ngā kitenga i puta, ā, he rerekē ngā aronga o aua kitenga, nō reira me whakamārama motuhake ia mea.

Tuatahi, i ora tonu ngā pūtau taketake mesenchymal, arā, te huinga kei roto hoki ngā pūtau ka hanga wheua ā muri ake, i ngā kukūtanga kahurangi metilīni me te mitokinōne mai i te 0.125 ki te 0.5 micromolar mō te 48 hāora. Kāore he paitini, kāore hoki he whakapainga. Tuarua, i te wā i whakaohohia ai aua pūtau taketake kia huri hei pūtau hanga wheua, arā, hei osteoblast, i roto i tētahi reo whakatipu hanga wheua, ā, i whakakano mō te phosphatase kawakore i te rā 18, kāore tētahi o ngā pūhui i whakarerekē i te hua i tētahi kukūtanga i whakamātauria. Kāore te taha hanga wheua o te rīhi i urupare.

Tuatoru, i urupare te taha wāwāhi wheua. I whakaohohia ngā pūtau tīmatanga o te hinu wheua ki te M-CSF me te RANKL, te tikanga paerewa mō te hanga osteoclast. I te pikinga o te kukūtanga, he iti ake ngā pūtau he maha ō rātou karihi, ā, he pai te tohu TRAP. I kitea te hekenga mārama i runga ake i te 0.25 micromolar, arā, i te kukūtanga teitei rawa i whakamātauria, te 0.5. Ko tēnei te kitenga e whakakaha ana i ngā whakarāpopototanga tūmanako maha, ā, he kitenga tūturu i roto i ōna rohenga: nā te pānga tōtika, haere tonu hoki i roto i te whakatipu pūtau i pēhi te hanganga osteoclast i runga i te nui o te horopeta.

Tuawhā, i tukuna ngā osteoblast kua pakari kia pā ki ngā pūhui mō te 48 hāora, kātahi ka whakamātauria mō te ahotea mitokōria. Kāore i kitea he rerekētanga whai tikanga ā-tatauranga i te whakamahinga hāora taketake, mōrahi rānei, mō tētahi o ngā pūhui. I te 0.5 micromolar, ko te āhua nei i whakaiti paku ngā pūhui e rua i te hā pūtau, engari kāore taua rerekētanga i whai tikanga ā-tatauranga. Nō reira, kāore te rīhi i whakaatu i tētahi whakaoranga mitokōria i ngā pūtau hanga wheua hei hoa mō te pānga pēhi osteoclast. Ko te tikanga i whakaarohia, arā, te whakapai ake i te mahi pūngao mā te mekameka kawe irahiko o te mitokōria, kāore i whakaputa i tētahi pikinga hā pūtau ka taea te ine i te wāhi i rapua ai e ngā kairangahau.

Ngā mea i puta i ngā kiore

E rua ngā whakamātautau kararehe i whai ake, ā, he tino rerekē te rahi o tētahi i tō tētahi.

I whakamahia e te whakamātautau iti ake ngā kiore uwha C57BL/6J nō te whakatipu whakapapa tata, he momo e whakamahia whānuitia ana i te rangahau koiora hauora. Mai i te 18 marama te pakeke, arā, he āhua rite ki te mutunga o te pakeketanga waenganui mō te kiore, i inu te haurua i te wai kei roto ko te 250 micromolar kahurangi metilīni mō te 6, te 12 marama rānei, tae noa ki te 24, te 30 marama rānei. Nā ngā uwha 18 marama kāore i hoatu he pūhui i whakarato te taumata tīmatanga, ā, nā ngā uwha 5 marama i whakaatu te āhua o ngā wheua taitamariki. I puta ngā pānga o te koroheketanga kia rite tonu ki te tūmanako. I te ira tuarā L5, i heke te hautanga rōrahi wheua mā te āhua 35 ōrau, te kiato kohuke mā te āhua 18 ōrau, ā, i heke te maha o ngā kurupae wheua moroiti ki te āhua haurua, ahakoa te maimoatanga. I heke te mātotoru o te wheua mārō o waho mā te āhua 10 ōrau i waenga i te 18 me te 24 marama, ā, mā te āhua 30 ōrau i te taenga ki te 30 marama. Kāore te kahurangi metilīni i whakarerekē i tētahi o ēnei ānau.

I whakahaerehia te whakamātautau nui ake mā te Interventions Testing Program a te National Institute on Aging. Ka whakamātau taua hōtaka i ngā pūhui kaitono ki ngā kiore UM-HET3 tāne me ngā uwha i ngā wāhi e toru. I tīmata te hoatu kahurangi metilīni ki te kai i te 28 wāhanga i ia miriona, me te mitokinōne i te 100 wāhanga i ia miriona, i te tīmatanga o te pakeketanga, ā, i haere tonu tae noa ki te āhua 22 ki te 24 marama te pakeke. I matawaingia aua wāhi kōiwi e toru anō mā te micro-CT. Ka whakaatu te ripanga i whakaputaina i ia tawhā mā te ira me te maimoatanga, me ngā tatauranga kua whakatikaina, ā, he ōrite te kōrero i te tīwae maimoatanga puta noa: kāore he pānga whai tikanga ā-tatauranga, kāore he pāhekoheko i waenga i te maimoatanga me te ira, i tētahi wāhi. Ahakoa te wheua mārō o waho, te wheua kōputaputa rānei; te wheua kūhā, te tuarā rānei; te tāne, te uwha rānei; te kahurangi metilīni, te mitokinōne rānei. I koroheketia tonu te kōiwi kia rite ki tōna tikanga.

Te ripanga whakataurite e hono ana i ngā haurua e rua

Ko tēnei te tūāpapa o te tuhinga katoa. Ka takirua ia rārangi i ngā mea i whakaaturia e te rīhi me ngā mea i whakaaturia e te kararehe mō taua tukanga koiora tonu, mā ngā inenga a te rangahau ake.

Ina pānuihia te ripanga i tēnā rārangi, i tēnā rārangi, ka ngaro te āhua taupatupatu. Kotahi anake o ngā tukanga pūtau e whā i urupare, ā, i urupare tata ki te pito teitei o te awhe i whakamātauria, i raro i te pānga tōtika, haere tonu hoki. Kāore kē he pānga ki ngā mea katoa atu i te rīhi. Nā reira, he iti ake te āhua taupatupatu o te hua kararehe, he nui ake tōna āhua whakaū: ko ngā hua kore pānga e toru, me tētahi pānga e herea ana ki ētahi āhuatanga i te whakatipu pūtau, i huri hei hua kore pānga puta noa i te kararehe.

He rerekē te hanganga wheua i te roa o te oranga

Me whai wāhanga motuhake tētahi pōhēhētanga, nā te mea he raraunga mō te kahurangi metilīni me te roa o te oranga, ā, he ngāwari te pānui hē i aua raraunga hei raraunga mō ngā wheua. I te rōpū o mua o te Interventions Testing Program, nā te kahurangi metilīni i taua horopeta kai tonu i whakapiki te roa o te oranga i te ōrau 90 o ngā uwha UM-HET3 mā te āhua 6 ōrau. He pānga ki te noho ora i te wāhanga whakamutunga o te oranga tēnei, kāore he rerekētanga ki te tau waenga o te roa o te oranga, kāore hoki he pānga ki ngā tāne. Kāore te mitokinōne i whakaatu i tētahi pānga ki te roa o te oranga i tētahi ira. I ahu mai aua tau noho ora i ngā pūkete roa o te oranga kua whakaputaina e te hōtaka, kāore i ahu mai i te pepa wheua.

Ko te takoha o te pepa wheua, he pupuri i ēnei huinga taunakitanga kia motuhake. Ka taea e tētahi pūhui te whakarerekē i te noho ora i te wāhanga whakamutunga o te oranga o tētahi ira, me te kore e tiaki i tētahi āhuatanga kōiwi i inea. Ka tatau ngā inenga noho ora i ngā matenga nā ngā take katoa; ka tatau te micro-CT i ngā kurupae moroiti o tētahi ira tuarā. Kāore he ture me mahi tētahi wawaotanga mā ngā wheua kia whakaroa ai te oranga. He taunakitanga tōtika tēnei rangahau i puta te tohu o te kahurangi metilīni mō te wāhanga whakamutunga o te oranga i ngā uwha mā tētahi atu ara. Ko te tangata e whakamahi ana i te kitenga roa o te oranga hei tautoko i te kahurangi metilīni mō te osteoporosis, e tango taunakitanga ana i te huinga hē. Ka kōrerohia te tikanga whānui o te wehe i ēnei huinga i te pānui i ngā rangahau kahurangi metilīni.

He aha i kore ai te rīhi e matapae i te hua kiore

E rima ngā whakamārama e hāngai ana ki ngā raraunga, ā, ka taea te hāngai o ētahi i te wā kotahi.

Ko te pānga o te pūhui te mea tuatahi. I rumakina tonutia ngā pūtau whakatipu ki ngā kukūtanga e mōhiotia ana. I kai ngā kiore i te kai kua tāpirihia te pūhui mō ngā marama maha, ā, kāore te rangahau i ine i ngā taumata pūhui i te hinu wheua, i tētahi tohu kino hāoratanga rānei i te wheua. Tērā pea kāore tētahi kukūtanga e pēhi ana i ngā osteoclast ina hoatu tōtikatia e tae atu ki ngā pūtau tīmatanga o te hinu wheua i taua taumata. Kotahi te horopeta mō ia pūhui i whakamātauria e te pepa i roto i ngā kararehe ora, nō reira kāore anō kia mōhiotia te urupare ki te horopeta i te kararehe.

Ko te matū te mea tuarua. Kāore ngā momo hāora tauhohe e noho hei huinga kotahi kua whakaranu pai ki roto i te pūtau. Ka mahi i roto i ngā wāhanga iti, mō ngā wā poto, ā, ka mahi motuhake ētahi wāhanga o ngā ara hāora-whakaheke o te mitokōria, te wai pūtau me ngā kiriuhi. Nā tōna hoahoa ka putu te mitokinōne ki roto i ngā mitokōria, engari ka taea e ngā tohu hāora e akiaki ana i te hanganga osteoclast te ahu mai i wāhi kē. Kāore te whakaiti i tētahi huinga e whai hua pēnei tonu i te rumaki haere tonu o te pūtau katoa.

Ko te hononga o ngā tukanga te mea tuatoru. I te wheua ora, e hono ana te wāwāhi me te hanga: ka tuku ngā osteoclast me ngā pūtau e noho tata ana i ngā tohu hei kukume mai i ngā pūtau hanga wheua ki te wāhi kātahi anō ka wāwāhia. Kāore te pēhi i te hanganga osteoclast e tāpiri aunoa i te nui ōrite o te wheua, nā te mea ka taea hoki e taua pēhitanga te whakakore i ngā tohu e karanga ana i ngā kaihanga. Kāore tētahi rīhi kei roto ko ngā pūtau tīmatanga anake e whakaatu i tēnei urupare whakahoki. Kāore e taea e tētahi kōiwi te huna.

Ko te utaina taumaha te mea tuawhā. Ka rongo ngā pūtau noho wheua, arā, ngā osteocyte, i te rerekētanga ā-miihini, ā, ka whakatakoto i te taurite whakahou mō te wheua katoa. I te koroheketanga o ngā kararehe me te hekenga o tō rātou nekeneke, ka ngoikore te tohu ā-miihini, ā, ka whai mai te ngaronga, ahakoa tētahi pānga rongoā iti ki tētahi momo pūtau kotahi. Ko ngā kaituhi tonu e tohu ana i te korikori tinana me te utaina taumaha hei whakaoho i te hanga kiko hei huarahi e nui ake ai te tūpono ki te whai pānga. He huarahi ātaahua tēnei ki te kī he kaha ake te urupare o te kōiwi ki te ahupūngao i tōna urupare ki te matū hāora-whakaheke.

Ko te wā tīmata te mea tuarima, engari he here tō tēnei whakamārama. I te whakamātautau C57BL/6J, i tīmata te maimoatanga i te 18 marama, i te wā kua nui kē te ngaronga hanganga. Kāore tētahi pūhui ārai wāwāhi wheua e hanga anō i ngā kurupae wheua moroiti kua kōhao, kua tangohia hoki, ki te kore he whakaoho hanga wheua e hāngai ana. Engari kāore e taea e te wā tīmata te whakamārama i te katoa, nā te mea i tīmata te hoatu horopeta o te Interventions Testing Program i te tīmatanga o te pakeketanga, ā, kāore tonu he mea i rerekē. Ka whakamārama te tīmatanga tōmuri i tētahi wāhanga o tētahi whakamātautau. Kāore e whakamārama i tētahi wāhanga o tērā atu.

Te tikanga o tēnei mō ngā kerēme kahurangi metilīni me te osteoporosis

Mō te kaipānui e aromātai ana i te kahurangi metilīni mō te hauora wheua, mō te koroheketanga kōiwi rānei, he poto te whakamāoritanga whaihua o ngā kitenga. E ai ki ngā taunakitanga kiore wā roa pai rawa e wātea ana, kāore he painga kōiwi i te hoatu kahurangi metilīni, mitokinōne rānei mō te wā roa, ahakoa he tohu pēhi osteoclast tūturu i te whakatipu pūtau. Ka whakaatu ngā tuhinga rangahau roa o te oranga i tētahi pānga iti o te kahurangi metilīni i te wāhanga whakamutunga o te oranga ki ngā uwha anake. E whakaatu ana tēnei rangahau kāore taua pānga i puta mā ngā wheua. Kāore tētahi o ēnei huinga taunakitanga e tautoko ana i te whakamahinga ki te tangata mō te osteoporosis, ā, kāore he raraunga wheua tangata i uru ki tēnei aromātai. Kei te haumaru me ngā pānga taha o te kahurangi metilīni ngā pātai mō te horopeta me te haumaru hua ki te tangata, kāore i tēnei kōiwi kiore.

Ko te akoranga hōhonu ake e pā ana ki te raupapa taunakitanga. Ko te hua pūtau he kōrero mō ngā mahi ka taea e tētahi pūhui ki tētahi momo pūtau kotahi i raro i te pānga whakahaerehia. Ko te hua wheua he kōrero mō ngā pānga o ngā marama o te tukunga ki te tinana katoa ki tētahi okana e hono ana i ngā momo pūtau e rua i raro i te mana ā-miihini. Ko te tuatahi te wāhi e whānau ai ngā whakapae. Ko te tuarua te wāhi i mutu ai tēnei whakapae mō te koroheketanga kōiwi me ēnei pūhui ārai hāoratanga e rua.